A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants
Identifieur interne : 002673 ( Pmc/Checkpoint ); précédent : 002672; suivant : 002674A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants
Auteurs : E. Theodoratou [Royaume-Uni] ; H. Campbell [Royaume-Uni] ; A. Tenesa [Royaume-Uni] ; R. Houlston [Royaume-Uni] ; E. Webb [Royaume-Uni] ; S. Lubbe [Royaume-Uni] ; P. Broderick [Royaume-Uni] ; S. Gallinger [Canada] ; E M Croitoru [Canada] ; M A Jenkins [Australie] ; A K Win [Australie] ; S P Cleary [Canada] ; T. Koessler [Royaume-Uni] ; P D Pharoah [Royaume-Uni] ; S. Küry [France] ; S. Bézieau [France] ; B. Buecher [France] ; N A Ellis [États-Unis] ; P. Peterlongo [Italie] ; K. Offit [États-Unis] ; L A Aaltonen [Finlande] ; S. Enholm [Finlande] ; A. Lindblom [Suède] ; X-L Zhou [Suède] ; I P Tomlinson [Royaume-Uni] ; V. Moreno [Espagne] ; I. Blanco [Espagne] ; G. Capellà [Espagne] ; R. Barnetson [Royaume-Uni] ; M E Porteous [Royaume-Uni] ; M G Dunlop [Royaume-Uni] ; S M Farrington [Royaume-Uni]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2010.
Abstract
Defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene
All three models produced very similar results.
Overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic
Url:
DOI: 10.1038/sj.bjc.6605966
PubMed: 21063410
PubMed Central: 3008602
Affiliations:
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Theodoratou</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Public Health Sciences, University of Edinburgh, Teviot Place</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Campbell, H" sort="Campbell, H" uniqKey="Campbell H" first="H" last="Campbell">H. Campbell</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Public Health Sciences, University of Edinburgh, Teviot Place</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tenesa, A" sort="Tenesa, A" uniqKey="Tenesa A" first="A" last="Tenesa">A. Tenesa</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Houlston, R" sort="Houlston, R" uniqKey="Houlston R" first="R" last="Houlston">R. Houlston</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Webb, E" sort="Webb, E" uniqKey="Webb E" first="E" last="Webb">E. Webb</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lubbe, S" sort="Lubbe, S" uniqKey="Lubbe S" first="S" last="Lubbe">S. Lubbe</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Broderick, P" sort="Broderick, P" uniqKey="Broderick P" first="P" last="Broderick">P. Broderick</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gallinger, S" sort="Gallinger, S" uniqKey="Gallinger S" first="S" last="Gallinger">S. Gallinger</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Ontario Familial Colorectal Cancer Registry</institution>, Toronto, Ontario,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Croitoru, E M" sort="Croitoru, E M" uniqKey="Croitoru E" first="E M" last="Croitoru">E M Croitoru</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, Toronto,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jenkins, M A" sort="Jenkins, M A" uniqKey="Jenkins M" first="M A" last="Jenkins">M A Jenkins</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Win, A K" sort="Win, A K" uniqKey="Win A" first="A K" last="Win">A K Win</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cleary, S P" sort="Cleary, S P" uniqKey="Cleary S" first="S P" last="Cleary">S P Cleary</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, Toronto,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koessler, T" sort="Koessler, T" uniqKey="Koessler T" first="T" last="Koessler">T. Koessler</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Strangeways Research Laboratory, Department of Oncology and Department of Public Health and Primary Care, University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pharoah, P D" sort="Pharoah, P D" uniqKey="Pharoah P" first="P D" last="Pharoah">P D Pharoah</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Strangeways Research Laboratory, Department of Oncology and Department of Public Health and Primary Care, University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kury, S" sort="Kury, S" uniqKey="Kury S" first="S" last="Küry">S. Küry</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>CHU de Nantes, pôle de Biologie, service de Génétique Médicale</institution>, 9 quai Moncousu, Nantes, 44093 cedex 1,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bezieau, S" sort="Bezieau, S" uniqKey="Bezieau S" first="S" last="Bézieau">S. Bézieau</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>CHU de Nantes, pôle de Biologie, service de Génétique Médicale</institution>, 9 quai Moncousu, Nantes, 44093 cedex 1,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Buecher, B" sort="Buecher, B" uniqKey="Buecher B" first="B" last="Buecher">B. Buecher</name><affiliation wicri:level="1"><nlm:aff id="aff10"><institution>unité de Génétique Constitutionnelle, Institut Curie, service de Génétique Oncologique</institution>, 26 rue d'Ulm, Paris, 75248 cedex 05,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ellis, N A" sort="Ellis, N A" uniqKey="Ellis N" first="N A" last="Ellis">N A Ellis</name><affiliation wicri:level="1"><nlm:aff id="aff11"><institution>University of Chicago</institution>, 900 East 57th Street, Chicago, IL 60637,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Peterlongo, P" sort="Peterlongo, P" uniqKey="Peterlongo P" first="P" last="Peterlongo">P. Peterlongo</name><affiliation wicri:level="1"><nlm:aff id="aff12"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori</institution>, Milan,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Offit, K" sort="Offit, K" uniqKey="Offit K" first="K" last="Offit">K. Offit</name><affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Clinical Cancer Genetics, Memorial Sloan-Kettering Cancer Centre</institution>, New York,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Aaltonen, L A" sort="Aaltonen, L A" uniqKey="Aaltonen L" first="L A" last="Aaltonen">L A Aaltonen</name><affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki</institution>, PO Box 63 (Haartmaninkatu 8), FIN-00014,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Enholm, S" sort="Enholm, S" uniqKey="Enholm S" first="S" last="Enholm">S. Enholm</name><affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki</institution>, PO Box 63 (Haartmaninkatu 8), FIN-00014,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Department of Molecular Medicine and Surgery Karolinska Institute and Department of Clinical Genetics Karolinska University Hospital</institution>, Stockholm,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, X L" sort="Zhou, X L" uniqKey="Zhou X" first="X-L" last="Zhou">X-L Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Department of Molecular Medicine and Surgery Karolinska Institute and Department of Clinical Genetics Karolinska University Hospital</institution>, Stockholm,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tomlinson, I P" sort="Tomlinson, I P" uniqKey="Tomlinson I" first="I P" last="Tomlinson">I P Tomlinson</name><affiliation wicri:level="1"><nlm:aff id="aff16"><institution>Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK</institution>, London,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moreno, V" sort="Moreno, V" uniqKey="Moreno V" first="V" last="Moreno">V. Moreno</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blanco, I" sort="Blanco, I" uniqKey="Blanco I" first="I" last="Blanco">I. Blanco</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capella, G" sort="Capella, G" uniqKey="Capella G" first="G" last="Capellà">G. Capellà</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Barnetson, R" sort="Barnetson, R" uniqKey="Barnetson R" first="R" last="Barnetson">R. Barnetson</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Porteous, M E" sort="Porteous, M E" uniqKey="Porteous M" first="M E" last="Porteous">M E Porteous</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Southeast of Scotland Clinical Genetic Services, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dunlop, M G" sort="Dunlop, M G" uniqKey="Dunlop M" first="M G" last="Dunlop">M G Dunlop</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Farrington, S M" sort="Farrington, S M" uniqKey="Farrington S" first="S M" last="Farrington">S M Farrington</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21063410</idno><idno type="pmc">3008602</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008602</idno><idno type="RBID">PMC:3008602</idno><idno type="doi">10.1038/sj.bjc.6605966</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000088</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000088</idno><idno type="wicri:Area/Pmc/Curation">000088</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000088</idno><idno type="wicri:Area/Pmc/Checkpoint">002673</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002673</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A large-scale meta-analysis to refine colorectal cancer risk estimates associated with <italic>MUTYH</italic> variants</title><author><name sortKey="Theodoratou, E" sort="Theodoratou, E" uniqKey="Theodoratou E" first="E" last="Theodoratou">E. Theodoratou</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Public Health Sciences, University of Edinburgh, Teviot Place</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Campbell, H" sort="Campbell, H" uniqKey="Campbell H" first="H" last="Campbell">H. Campbell</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Public Health Sciences, University of Edinburgh, Teviot Place</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tenesa, A" sort="Tenesa, A" uniqKey="Tenesa A" first="A" last="Tenesa">A. Tenesa</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Houlston, R" sort="Houlston, R" uniqKey="Houlston R" first="R" last="Houlston">R. Houlston</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Webb, E" sort="Webb, E" uniqKey="Webb E" first="E" last="Webb">E. Webb</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lubbe, S" sort="Lubbe, S" uniqKey="Lubbe S" first="S" last="Lubbe">S. Lubbe</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Broderick, P" sort="Broderick, P" uniqKey="Broderick P" first="P" last="Broderick">P. Broderick</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gallinger, S" sort="Gallinger, S" uniqKey="Gallinger S" first="S" last="Gallinger">S. Gallinger</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Ontario Familial Colorectal Cancer Registry</institution>, Toronto, Ontario,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Croitoru, E M" sort="Croitoru, E M" uniqKey="Croitoru E" first="E M" last="Croitoru">E M Croitoru</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, Toronto,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jenkins, M A" sort="Jenkins, M A" uniqKey="Jenkins M" first="M A" last="Jenkins">M A Jenkins</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Win, A K" sort="Win, A K" uniqKey="Win A" first="A K" last="Win">A K Win</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cleary, S P" sort="Cleary, S P" uniqKey="Cleary S" first="S P" last="Cleary">S P Cleary</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, Toronto,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koessler, T" sort="Koessler, T" uniqKey="Koessler T" first="T" last="Koessler">T. Koessler</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Strangeways Research Laboratory, Department of Oncology and Department of Public Health and Primary Care, University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pharoah, P D" sort="Pharoah, P D" uniqKey="Pharoah P" first="P D" last="Pharoah">P D Pharoah</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Strangeways Research Laboratory, Department of Oncology and Department of Public Health and Primary Care, University of Cambridge</institution>, Cambridge,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kury, S" sort="Kury, S" uniqKey="Kury S" first="S" last="Küry">S. Küry</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>CHU de Nantes, pôle de Biologie, service de Génétique Médicale</institution>, 9 quai Moncousu, Nantes, 44093 cedex 1,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bezieau, S" sort="Bezieau, S" uniqKey="Bezieau S" first="S" last="Bézieau">S. Bézieau</name><affiliation wicri:level="1"><nlm:aff id="aff9"><institution>CHU de Nantes, pôle de Biologie, service de Génétique Médicale</institution>, 9 quai Moncousu, Nantes, 44093 cedex 1,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Buecher, B" sort="Buecher, B" uniqKey="Buecher B" first="B" last="Buecher">B. Buecher</name><affiliation wicri:level="1"><nlm:aff id="aff10"><institution>unité de Génétique Constitutionnelle, Institut Curie, service de Génétique Oncologique</institution>, 26 rue d'Ulm, Paris, 75248 cedex 05,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ellis, N A" sort="Ellis, N A" uniqKey="Ellis N" first="N A" last="Ellis">N A Ellis</name><affiliation wicri:level="1"><nlm:aff id="aff11"><institution>University of Chicago</institution>, 900 East 57th Street, Chicago, IL 60637,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Peterlongo, P" sort="Peterlongo, P" uniqKey="Peterlongo P" first="P" last="Peterlongo">P. Peterlongo</name><affiliation wicri:level="1"><nlm:aff id="aff12"><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori</institution>, Milan,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Offit, K" sort="Offit, K" uniqKey="Offit K" first="K" last="Offit">K. Offit</name><affiliation wicri:level="1"><nlm:aff id="aff13"><institution>Clinical Cancer Genetics, Memorial Sloan-Kettering Cancer Centre</institution>, New York,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Aaltonen, L A" sort="Aaltonen, L A" uniqKey="Aaltonen L" first="L A" last="Aaltonen">L A Aaltonen</name><affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki</institution>, PO Box 63 (Haartmaninkatu 8), FIN-00014,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Enholm, S" sort="Enholm, S" uniqKey="Enholm S" first="S" last="Enholm">S. Enholm</name><affiliation wicri:level="1"><nlm:aff id="aff14"><institution>Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki</institution>, PO Box 63 (Haartmaninkatu 8), FIN-00014,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name><affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Department of Molecular Medicine and Surgery Karolinska Institute and Department of Clinical Genetics Karolinska University Hospital</institution>, Stockholm,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, X L" sort="Zhou, X L" uniqKey="Zhou X" first="X-L" last="Zhou">X-L Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff15"><institution>Department of Molecular Medicine and Surgery Karolinska Institute and Department of Clinical Genetics Karolinska University Hospital</institution>, Stockholm,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tomlinson, I P" sort="Tomlinson, I P" uniqKey="Tomlinson I" first="I P" last="Tomlinson">I P Tomlinson</name><affiliation wicri:level="1"><nlm:aff id="aff16"><institution>Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK</institution>, London,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moreno, V" sort="Moreno, V" uniqKey="Moreno V" first="V" last="Moreno">V. Moreno</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blanco, I" sort="Blanco, I" uniqKey="Blanco I" first="I" last="Blanco">I. Blanco</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Capella, G" sort="Capella, G" uniqKey="Capella G" first="G" last="Capellà">G. Capellà</name><affiliation wicri:level="1"><nlm:aff id="aff17"><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Barnetson, R" sort="Barnetson, R" uniqKey="Barnetson R" first="R" last="Barnetson">R. Barnetson</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Porteous, M E" sort="Porteous, M E" uniqKey="Porteous M" first="M E" last="Porteous">M E Porteous</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Southeast of Scotland Clinical Genetic Services, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dunlop, M G" sort="Dunlop, M G" uniqKey="Dunlop M" first="M G" last="Dunlop">M G Dunlop</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Farrington, S M" sort="Farrington, S M" uniqKey="Farrington S" first="S M" last="Farrington">S M Farrington</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>Defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene <italic>MUTYH</italic> are responsible for <italic>MUTYH</italic>-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested <italic>MUTYH</italic> mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic <italic>MUTYH</italic> variants and investigate age and sex influence on risk.</p></sec><sec><title>Methods:</title><p><italic>MUTYH</italic> genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study.</p></sec><sec><title>Results:</title><p>All three models produced very similar results. <italic>MUTYH</italic> bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95–115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00–1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for <italic>MUTYH</italic>, G396D and Y179C (OR=10.8, 95% CI: 5.02–23.2; OR=6.47, 95% CI: 2.33–18.0; OR=3.35, 95% CI: 1.14–9.89) and marginal mono-allelic effect for variants <italic>MUTYH</italic> (OR=1.16, 95% CI: 1.00–1.34) and Y179C alone (OR=1.34, 95% CI: 1.01–1.77).</p></sec><sec><title>Conclusions:</title><p>Overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic <italic>MUTYH</italic> carriers.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Al Tassan, N" uniqKey="Al Tassan N">N Al-Tassan</name></author><author><name sortKey="Chmiel, Nh" uniqKey="Chmiel N">NH Chmiel</name></author><author><name sortKey="Maynard, J" uniqKey="Maynard J">J Maynard</name></author><author><name sortKey="Fleming, N" uniqKey="Fleming N">N Fleming</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id><journal-title-group><journal-title>British Journal of Cancer</journal-title></journal-title-group><issn pub-type="ppub">0007-0920</issn><issn pub-type="epub">1532-1827</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21063410</article-id><article-id pub-id-type="pmc">3008602</article-id><article-id pub-id-type="pii">6605966</article-id><article-id pub-id-type="doi">10.1038/sj.bjc.6605966</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics and Genomics</subject></subj-group></article-categories><title-group><article-title>A large-scale meta-analysis to refine colorectal cancer risk estimates associated with <italic>MUTYH</italic> variants</article-title><alt-title alt-title-type="running">Collaborative <italic>MUTYH</italic> risk analysis</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Theodoratou</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Campbell</surname><given-names>H</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tenesa</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Houlston</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Webb</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="author-notes" rid="note1"><sup>18</sup></xref></contrib><contrib 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contrib-type="author"><name><surname>Peterlongo</surname><given-names>P</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author"><name><surname>Offit</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Aaltonen</surname><given-names>L A</given-names></name><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Enholm</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Lindblom</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Zhou</surname><given-names>X-L</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Tomlinson</surname><given-names>I P</given-names></name><xref ref-type="aff" rid="aff16">16</xref></contrib><contrib contrib-type="author"><name><surname>Moreno</surname><given-names>V</given-names></name><xref ref-type="aff" rid="aff17">17</xref></contrib><contrib contrib-type="author"><name><surname>Blanco</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff17">17</xref></contrib><contrib contrib-type="author"><name><surname>Capellà</surname><given-names>G</given-names></name><xref ref-type="aff" rid="aff17">17</xref></contrib><contrib contrib-type="author"><name><surname>Barnetson</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Porteous</surname><given-names>M E</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Dunlop</surname><given-names>M G</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Farrington</surname><given-names>S M</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><aff id="aff1"><label>1</label><institution>Colon Cancer Genetics Group and Academic Coloproctology, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh</institution>, Edinburgh,<country>UK</country></aff><aff id="aff2"><label>2</label><institution>Public Health Sciences, University of Edinburgh, Teviot Place</institution>, Edinburgh,<country>UK</country></aff><aff id="aff3"><label>3</label><institution>Southeast of Scotland Clinical Genetic Services, University of Edinburgh</institution>, Edinburgh,<country>UK</country></aff><aff id="aff4"><label>4</label><institution>Section of Cancer Genetics, Institute of Cancer Research</institution>, Sutton, Surrey,<country>UK</country></aff><aff id="aff5"><label>5</label><institution>Ontario Familial Colorectal Cancer Registry</institution>, Toronto, Ontario,<country>Canada</country></aff><aff id="aff6"><label>6</label><institution>Samuel Lunenfeld Research Institute, Mount Sinai Hospital</institution>, Toronto,<country>Canada</country></aff><aff id="aff7"><label>7</label><institution>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne</institution>, Victoria,<country>Australia</country></aff><aff id="aff8"><label>8</label><institution>Strangeways Research Laboratory, Department of Oncology and Department of Public Health and Primary Care, University of Cambridge</institution>, Cambridge,<country>UK</country></aff><aff id="aff9"><label>9</label><institution>CHU de Nantes, pôle de Biologie, service de Génétique Médicale</institution>, 9 quai Moncousu, Nantes, 44093 cedex 1,<country>France</country></aff><aff id="aff10"><label>10</label><institution>unité de Génétique Constitutionnelle, Institut Curie, service de Génétique Oncologique</institution>, 26 rue d'Ulm, Paris, 75248 cedex 05,<country>France</country></aff><aff id="aff11"><label>11</label><institution>University of Chicago</institution>, 900 East 57th Street, Chicago, IL 60637,<country>USA</country></aff><aff id="aff12"><label>12</label><institution>IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori</institution>, Milan,<country>Italy</country></aff><aff id="aff13"><label>13</label><institution>Clinical Cancer Genetics, Memorial Sloan-Kettering Cancer Centre</institution>, New York,<country>USA</country></aff><aff id="aff14"><label>14</label><institution>Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki</institution>, PO Box 63 (Haartmaninkatu 8), FIN-00014,<country>Finland</country></aff><aff id="aff15"><label>15</label><institution>Department of Molecular Medicine and Surgery Karolinska Institute and Department of Clinical Genetics Karolinska University Hospital</institution>, Stockholm,<country>Sweden</country></aff><aff id="aff16"><label>16</label><institution>Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK</institution>, London,<country>UK</country></aff><aff id="aff17"><label>17</label><institution>Catalan Institute of Oncology-ICO, IDIBELL and University of Barcelona</institution>, Av Gran Via 199, L'Hospitalet, Barcelona 08907,<country>Spain</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label>E-mail: <email>Susan.Farrington@hgu.mrc.ac.uk</email></corresp><fn fn-type="present-address" id="note1"><label>18</label><p>Present address: Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK</p></fn></author-notes><pub-date pub-type="ppub"><day>07</day><month>12</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>09</day><month>11</month><year>2010</year></pub-date><volume>103</volume><issue>12</issue><fpage>1875</fpage><lpage>1884</lpage><history><date date-type="received"><day>02</day><month>07</month><year>2010</year></date><date date-type="rev-recd"><day>16</day><month>09</month><year>2010</year></date><date date-type="accepted"><day>30</day><month>09</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © 2010 Cancer Research UK</copyright-statement><copyright-year>2010</copyright-year><copyright-holder>Cancer Research UK</copyright-holder></permissions><abstract><sec><title>Background:</title><p>Defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene <italic>MUTYH</italic> are responsible for <italic>MUTYH</italic>-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested <italic>MUTYH</italic> mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic <italic>MUTYH</italic> variants and investigate age and sex influence on risk.</p></sec><sec><title>Methods:</title><p><italic>MUTYH</italic> genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study.</p></sec><sec><title>Results:</title><p>All three models produced very similar results. <italic>MUTYH</italic> bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95–115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00–1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for <italic>MUTYH</italic>, G396D and Y179C (OR=10.8, 95% CI: 5.02–23.2; OR=6.47, 95% CI: 2.33–18.0; OR=3.35, 95% CI: 1.14–9.89) and marginal mono-allelic effect for variants <italic>MUTYH</italic> (OR=1.16, 95% CI: 1.00–1.34) and Y179C alone (OR=1.34, 95% CI: 1.01–1.77).</p></sec><sec><title>Conclusions:</title><p>Overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic <italic>MUTYH</italic> carriers.</p></sec></abstract><kwd-group><kwd>colorectal cancer</kwd><kwd>base excision repair</kwd><kwd><italic>MUTYH</italic></kwd><kwd>carrier risk estimates</kwd><kwd>meta-analysis</kwd></kwd-group></article-meta></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>Meta-analysis of studies comparing <italic>MUTYH</italic> MM <italic>vs</italic> WW. SOCCS data include <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006</xref>) and unpublished data from the SOCCS study obtained in 2008; Cleary data include <xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref>; Lubbe data include <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>. Unpublished studies included are Tomilson I (2006) and Koessler T (2007).</p></caption><graphic xlink:href="6605966f1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Meta-analysis of studies comparing <italic>MUTYH</italic> WM <italic>vs</italic> WW. SOCCS data include <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006)</xref> and unpublished data from the SOCCS study obtained in 2008; Cleary data include <xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref>; Lubbe data include <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>. Unpublished studies included are Tomilson I (2006) and Koessler T (2007).</p></caption><graphic xlink:href="6605966f2"></graphic></fig><table-wrap id="tbl1"><label>Table 1</label><caption><title>Summary table<xref ref-type="fn" rid="t1-fn2">a</xref></title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>G396D</bold></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Y179C</bold></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Genotype</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Age</bold></th><th colspan="2" align="center" valign="top" char="(" charoff="50"><bold>Sex</bold></th><th colspan="3" align="center" valign="top" char="(" charoff="50"><bold>Ethnicity</bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Study</bold></th><th align="center" valign="top" char="." charoff="50"><bold>Number</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WW</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WM</bold></th><th align="center" valign="top" char="." charoff="50"><bold>MM</bold></th><th align="center" valign="top" char="(" charoff="50"><bold><italic>n</italic> (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Mean (SD)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold><italic>n</italic> (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Males (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold><italic>n</italic> (%)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>Caucasian/White (%)</bold></th></tr></thead><tbody valign="top"><tr><td colspan="17" align="left" valign="top" charoff="50">All studies</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">20 565</td><td align="char" valign="top" char="." charoff="50">19 966</td><td align="char" valign="top" char="." charoff="50">324</td><td align="char" valign="top" char="." charoff="50">33</td><td align="char" valign="top" char="." charoff="50">20 260</td><td align="char" valign="top" char="." charoff="50">154</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">19 783</td><td align="char" valign="top" char="." charoff="50">417</td><td align="char" valign="top" char="." charoff="50">76</td><td align="char" valign="top" char="(" charoff="50">20 555 (99.9)</td><td align="char" valign="top" char="(" charoff="50">59.5 (10.1)</td><td align="char" valign="top" char="(" charoff="50">20 555 (99.9)</td><td align="char" valign="top" char="(" charoff="50">11 668 (56.8)</td><td align="char" valign="top" char="(" charoff="50">5374 (26.1)</td><td align="char" valign="top" char="(" charoff="50">5030 (93.6)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">15 524</td><td align="char" valign="top" char="." charoff="50">15 145</td><td align="char" valign="top" char="." charoff="50">211</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">15 074</td><td align="char" valign="top" char="." charoff="50">68</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">14 723</td><td align="char" valign="top" char="." charoff="50">280</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="(" charoff="50">15 287 (98.5)</td><td align="char" valign="top" char="(" charoff="50">59.0 (10.9)</td><td align="char" valign="top" char="(" charoff="50">15 521 (99.9)</td><td align="char" valign="top" char="(" charoff="50">6845 (44.1)</td><td align="char" valign="top" char="(" charoff="50">5597 (36.1)</td><td align="char" valign="top" char="(" charoff="50">4796 (85.7)</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">1238</td><td align="char" valign="top" char="." charoff="50">1209</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">1223</td><td align="char" valign="top" char="." charoff="50">13</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">1197</td><td align="char" valign="top" char="." charoff="50">29</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="(" charoff="50">1236 (99.8)</td><td align="char" valign="top" char="(" charoff="50">60.1 (8.7)</td><td align="char" valign="top" char="(" charoff="50">1236 (99.8)</td><td align="char" valign="top" char="(" charoff="50">544 (44.0)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">1255</td><td align="char" valign="top" char="." charoff="50">1238</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1251</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1234</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1244 (99.1)</td><td align="char" valign="top" char="(" charoff="50">63.6 (8.6)</td><td align="char" valign="top" char="(" charoff="50">1252 (99.8)</td><td align="char" valign="top" char="(" charoff="50">702 (56.1)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib22">Peterlongo <italic>et al</italic> (2005)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">585</td><td align="char" valign="top" char="." charoff="50">567</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">569</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">552</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="(" charoff="50">584 (99.8)</td><td align="char" valign="top" char="(" charoff="50">62.1 (13.1)</td><td align="char" valign="top" char="(" charoff="50">584 (99.8)</td><td align="char" valign="top" char="(" charoff="50">319 (54.6)</td><td align="char" valign="top" char="(" charoff="50">585 (100)</td><td align="char" valign="top" char="(" charoff="50">251 (42.9)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">1158</td><td align="char" valign="top" char="." charoff="50">1040</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1039</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">923</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1148 (99.1)</td><td align="char" valign="top" char="(" charoff="50">53.9 (11.5)</td><td align="char" valign="top" char="(" charoff="50">1156 (99.8)</td><td align="char" valign="top" char="(" charoff="50">240 (20.8)</td><td align="char" valign="top" char="(" charoff="50">1158 (100)</td><td align="char" valign="top" char="(" charoff="50">363 (31.3)</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50">SOCCS (includes data from <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006)</xref> and unpublished SOCCS prospective samples)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">3278</td><td align="char" valign="top" char="." charoff="50">3086</td><td align="char" valign="top" char="." charoff="50">55</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">3192</td><td align="char" valign="top" char="." charoff="50">23</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">3038</td><td align="char" valign="top" char="." charoff="50">71</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="(" charoff="50">3277 (100)</td><td align="char" valign="top" char="(" charoff="50">59.5 (11.3)</td><td align="char" valign="top" char="(" charoff="50">3278 (100)</td><td align="char" valign="top" char="(" charoff="50">1883 (57.4)</td><td align="char" valign="top" char="(" charoff="50">3278 (100)</td><td align="char" valign="top" char="(" charoff="50">3268 (99.7)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">3318</td><td align="char" valign="top" char="." charoff="50">3239</td><td align="char" valign="top" char="." charoff="50">43</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">3061</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">2993</td><td align="char" valign="top" char="." charoff="50">57</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">3313 (99.8)</td><td align="char" valign="top" char="(" charoff="50">61.4 (10.9)</td><td align="char" valign="top" char="(" charoff="50">3318 (100)</td><td align="char" valign="top" char="(" charoff="50">1861 (56.1)</td><td align="char" valign="top" char="(" charoff="50">3318 (100)</td><td align="char" valign="top" char="(" charoff="50">3312 (99.8)</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib19">Moreno <italic>et al</italic> (2006)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">356</td><td align="char" valign="top" char="." charoff="50">343</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">348</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">336</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">356 (100)</td><td align="char" valign="top" char="(" charoff="50">66.5 (11.7)</td><td align="char" valign="top" char="(" charoff="50">356 (100)</td><td align="char" valign="top" char="(" charoff="50">217 (61.0)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">297</td><td align="char" valign="top" char="." charoff="50">285</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">291</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">283</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">297 (100)</td><td align="char" valign="top" char="(" charoff="50">65.3 (12.5)</td><td align="char" valign="top" char="(" charoff="50">297 (100)</td><td align="char" valign="top" char="(" charoff="50">158 (53.2)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50">Koessler T, (unpublished data obtained in 2007)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">2262</td><td align="char" valign="top" char="." charoff="50">2215</td><td align="char" valign="top" char="." charoff="50">31</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">2227</td><td align="char" valign="top" char="." charoff="50">19</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">2198</td><td align="char" valign="top" char="." charoff="50">37</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="(" charoff="50">2253 (99.6)</td><td align="char" valign="top" char="(" charoff="50">59.1 (8.1)</td><td align="char" valign="top" char="(" charoff="50">2262 (100)</td><td align="char" valign="top" char="(" charoff="50">1287 (57.1)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">2253</td><td align="char" valign="top" char="." charoff="50">2217</td><td align="char" valign="top" char="." charoff="50">31</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">2236</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">2204</td><td align="char" valign="top" char="." charoff="50">42</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">2053 (91.1)</td><td align="char" valign="top" char="(" charoff="50">53.4 (7.6)</td><td align="char" valign="top" char="(" charoff="50">2253 (100)</td><td align="char" valign="top" char="(" charoff="50">949 (42.0)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib17">Küry <italic>et al</italic> (2007)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">1025</td><td align="char" valign="top" char="." charoff="50">1003</td><td align="char" valign="top" char="." charoff="50">22</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1021</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">999</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1023 (99.8)</td><td align="char" valign="top" char="(" charoff="50">68.7 (9.9)</td><td align="char" valign="top" char="(" charoff="50">1025 (100)</td><td align="char" valign="top" char="(" charoff="50">632 (61.7)</td><td align="char" valign="top" char="(" charoff="50">1025 (100)</td><td align="char" valign="top" char="(" charoff="50">1025 (100)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">1121</td><td align="char" valign="top" char="." charoff="50">1105</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1117</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1100</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1121 (100)</td><td align="char" valign="top" char="(" charoff="50">61.9 (10.0)</td><td align="char" valign="top" char="(" charoff="50">1121 (100)</td><td align="char" valign="top" char="(" charoff="50">609 (54.3)</td><td align="char" valign="top" char="(" charoff="50">1121 (100)</td><td align="char" valign="top" char="(" charoff="50">1121 (100)</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50">SOCCS retrospective cases (unpublished data obtained in 2008)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">486</td><td align="char" valign="top" char="." charoff="50">403</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">446</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">391</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="(" charoff="50">486 (100)</td><td align="char" valign="top" char="(" charoff="50">54.7 (17.2)</td><td align="char" valign="top" char="(" charoff="50">479 (98.6)</td><td align="char" valign="top" char="(" charoff="50">240 (50.1)</td><td align="char" valign="top" char="(" charoff="50">486 (100)</td><td align="char" valign="top" char="(" charoff="50">486 (100)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0</td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0</td><td align="char" valign="top" char="(" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib5">Cleary <italic>et al</italic> (2009)</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">2076</td><td align="char" valign="top" char="." charoff="50">2023</td><td align="char" valign="top" char="." charoff="50">33</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">2053</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">2029</td><td align="char" valign="top" char="." charoff="50">38</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="(" charoff="50">2070 (99.7)</td><td align="char" valign="top" char="(" charoff="50">56.6 (10.8)</td><td align="char" valign="top" char="(" charoff="50">2076 (100)</td><td align="char" valign="top" char="(" charoff="50">1114 (53.7)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">1049</td><td align="char" valign="top" char="." charoff="50">1032</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1042</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">1024</td><td align="char" valign="top" char="." charoff="50">24</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1047 (99.8)</td><td align="char" valign="top" char="(" charoff="50">56.4 (11.3)</td><td align="char" valign="top" char="(" charoff="50">1049 (100)</td><td align="char" valign="top" char="(" charoff="50">444 (42.3)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing</td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="17" align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib18">Lubbe <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t1-fn3">b</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Cases</italic></td><td align="char" valign="top" char="." charoff="50">9268</td><td align="char" valign="top" char="." charoff="50">9117</td><td align="char" valign="top" char="." charoff="50">141</td><td align="char" valign="top" char="." charoff="50">10</td><td align="char" valign="top" char="." charoff="50">9181</td><td align="char" valign="top" char="." charoff="50">83</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">9043</td><td align="char" valign="top" char="." charoff="50">198</td><td align="char" valign="top" char="." charoff="50">27</td><td align="char" valign="top" char="(" charoff="50">9268 (100)</td><td align="char" valign="top" char="(" charoff="50">59.0 (8.5)</td><td align="char" valign="top" char="(" charoff="50">9268 (100)</td><td align="char" valign="top" char="(" charoff="50">5432 (58.6)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing<xref ref-type="fn" rid="t1-fn4">c</xref></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>Controls</italic></td><td align="char" valign="top" char="." charoff="50">5064</td><td align="char" valign="top" char="." charoff="50">4989</td><td align="char" valign="top" char="." charoff="50">75</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">5037</td><td align="char" valign="top" char="." charoff="50">26</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">4962</td><td align="char" valign="top" char="." charoff="50">101</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">5064 (100)</td><td align="char" valign="top" char="(" charoff="50">59.2 (10.8)</td><td align="char" valign="top" char="(" charoff="50">5064 (100)</td><td align="char" valign="top" char="(" charoff="50">1882 (37.2)</td><td align="char" valign="top" char="(" charoff="50">Missing</td><td align="char" valign="top" char="(" charoff="50">Missing<xref ref-type="fn" rid="t1-fn4">c</xref></td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>Abbreviations: MM=mutated/mutated; WM=wild type/mutant; WW=wild type/wild type.</p></fn><fn id="t1-fn2"><label>a</label><p>This table presents the raw data sent to us by each group that was then included in the analyses. G396D and Y179C are looked at independently and any compound bi-allelic carriers are presented as heterozygotes for each variant; MUTYH genotype data also includes other pathogenic mutations; unpublished data are included in Peterlonogo P and Moreno V, SOCCS prospective and Küry S.</p></fn><fn id="t1-fn3"><label>b</label><p>Includes data from <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>.</p></fn><fn id="t1-fn4"><label>c</label><p>All the cases and controls were UK residents and of European ancestry (self-reported).</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Logistic regression analysis of the combined datasets; G396D analysis was conducted for individuals that were Y179C AA; Y179C analysis was conducted for individuals that were G396D GG; combined genotype analysis was conducted for individuals with data for both Y179C and G396D</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th align="char" valign="top" char="." charoff="50"> </th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Model I</bold><bold>*</bold><sup>,</sup><xref ref-type="fn" rid="t2-fn3">a</xref></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Model I</bold><xref ref-type="fn" rid="t2-fn4">b</xref></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Gene</bold></th><th align="center" valign="top" char="." charoff="50"><bold>Cases</bold></th><th align="center" valign="top" char="." charoff="50"><bold>Controls</bold></th><th align="center" valign="top" char="." charoff="50"><bold>OR</bold></th><th align="center" valign="top" char="." charoff="50"><bold>95% CI</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>P</italic>-value</bold></th><th align="center" valign="top" char="." charoff="50"><bold>OR</bold></th><th align="center" valign="top" char="." charoff="50"><bold>95% CI</bold></th><th align="center" valign="top" char="." charoff="50"><bold><italic>P</italic>-value</bold></th></tr></thead><tbody valign="top"><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>G396D</italic><xref ref-type="fn" rid="t2-fn5">c</xref></td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Whole sample</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">19 767</td><td align="char" valign="top" char="." charoff="50">14 723</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GA</td><td align="char" valign="top" char="." charoff="50">292</td><td align="char" valign="top" char="." charoff="50">210</td><td align="char" valign="top" char="." charoff="50">1.04</td><td align="char" valign="top" char="." charoff="50">0.87, 1.24</td><td align="char" valign="top" char="." charoff="50">0.70</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">31</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">23.09</td><td align="char" valign="top" char="." charoff="50">3.15, 169.15</td><td align="char" valign="top" char="." charoff="50">0.002</td><td align="char" valign="top" char="." charoff="50">46.93</td><td align="char" valign="top" char="." charoff="50">2.87, 766.89</td><td align="char" valign="top" char="." charoff="50">0.007</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ⩽<italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">6269</td><td align="char" valign="top" char="." charoff="50">5270</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GA</td><td align="char" valign="top" char="." charoff="50">88</td><td align="char" valign="top" char="." charoff="50">77</td><td align="char" valign="top" char="." charoff="50">0.96</td><td align="char" valign="top" char="." charoff="50">0.71, 1.31</td><td align="char" valign="top" char="." charoff="50">0.80</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">13</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">10.93</td><td align="char" valign="top" char="." charoff="50">1.43, 83.57</td><td align="char" valign="top" char="." charoff="50">0.02</td><td align="char" valign="top" char="." charoff="50">22.70</td><td align="char" valign="top" char="." charoff="50">1.35, 381.91</td><td align="char" valign="top" char="." charoff="50">0.03</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ><italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">13 498</td><td align="char" valign="top" char="." charoff="50">9453</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GA</td><td align="char" valign="top" char="." charoff="50">204</td><td align="char" valign="top" char="." charoff="50">133</td><td align="char" valign="top" char="." charoff="50">1.07</td><td align="char" valign="top" char="." charoff="50">0.86, 1.34</td><td align="char" valign="top" char="." charoff="50">0.52</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">12.60</td><td align="char" valign="top" char="." charoff="50">1.68, 94.37</td><td align="char" valign="top" char="." charoff="50">0.01</td><td align="char" valign="top" char="." charoff="50">25.91</td><td align="char" valign="top" char="." charoff="50">1.56, 430.03</td><td align="char" valign="top" char="." charoff="50">0.02</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Males</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">11 229</td><td align="char" valign="top" char="." charoff="50">6460</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GA</td><td align="char" valign="top" char="." charoff="50">161</td><td align="char" valign="top" char="." charoff="50">95</td><td align="char" valign="top" char="." charoff="50">0.98</td><td align="char" valign="top" char="." charoff="50">0.76, 1.26</td><td align="char" valign="top" char="." charoff="50">0.85</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">8.62</td><td align="char" valign="top" char="." charoff="50">1.14, 65.25</td><td align="char" valign="top" char="." charoff="50">0.04</td><td align="char" valign="top" char="." charoff="50">17.84</td><td align="char" valign="top" char="." charoff="50">1.07, 298.11</td><td align="char" valign="top" char="." charoff="50">0.04</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Females</italic></td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">8528</td><td align="char" valign="top" char="." charoff="50">8259</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GA</td><td align="char" valign="top" char="." charoff="50">131</td><td align="char" valign="top" char="." charoff="50">115</td><td align="char" valign="top" char="." charoff="50">1.10</td><td align="char" valign="top" char="." charoff="50">0.86, 1.42</td><td align="char" valign="top" char="." charoff="50">0.45</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">15.49</td><td align="char" valign="top" char="." charoff="50">2.05, 116.86</td><td align="char" valign="top" char="." charoff="50">0.008</td><td align="char" valign="top" char="." charoff="50">31.96</td><td align="char" valign="top" char="." charoff="50">1.92, 532.72</td><td align="char" valign="top" char="." charoff="50">0.02</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Y179C</italic><xref ref-type="fn" rid="t2-fn6">d</xref></td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Whole sample</italic></td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">19 767</td><td align="char" valign="top" char="." charoff="50">14 723</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AG</td><td align="char" valign="top" char="." charoff="50">122</td><td align="char" valign="top" char="." charoff="50">68</td><td align="char" valign="top" char="." charoff="50">1.34</td><td align="char" valign="top" char="." charoff="50">1.00, 1.80</td><td align="char" valign="top" char="." charoff="50">0.05</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">4.10</td><td align="char" valign="top" char="." charoff="50">0.91, 18.48</td><td align="char" valign="top" char="." charoff="50">0.07</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ⩽<italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">6269</td><td align="char" valign="top" char="." charoff="50">5270</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AG</td><td align="char" valign="top" char="." charoff="50">35</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">1.18</td><td align="char" valign="top" char="." charoff="50">0.70, 1.97</td><td align="char" valign="top" char="." charoff="50">0.54</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">7.57</td><td align="char" valign="top" char="." charoff="50">0.96, 59.74</td><td align="char" valign="top" char="." charoff="50">0.06</td><td align="char" valign="top" char="." charoff="50">15.97</td><td align="char" valign="top" char="." charoff="50">0.93, 274.491</td><td align="char" valign="top" char="." charoff="50">0.06</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ><italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">13 498</td><td align="char" valign="top" char="." charoff="50">9453</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AG</td><td align="char" valign="top" char="." charoff="50">87</td><td align="char" valign="top" char="." charoff="50">43</td><td align="char" valign="top" char="." charoff="50">1.42</td><td align="char" valign="top" char="." charoff="50">0.98, 2.04</td><td align="char" valign="top" char="." charoff="50">0.06</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0.70</td><td align="char" valign="top" char="." charoff="50">0.10, 4.97</td><td align="char" valign="top" char="." charoff="50">0.72</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Males</italic></td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">11 229</td><td align="char" valign="top" char="." charoff="50">6460</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AG</td><td align="char" valign="top" char="." charoff="50">68</td><td align="char" valign="top" char="." charoff="50">23</td><td align="char" valign="top" char="." charoff="50">1.70</td><td align="char" valign="top" char="." charoff="50">1.06, 2.73</td><td align="char" valign="top" char="." charoff="50">0.03</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">4.60</td><td align="char" valign="top" char="." charoff="50">0.58, 36.80</td><td align="char" valign="top" char="." charoff="50">0.15</td><td align="char" valign="top" char="." charoff="50">9.78</td><td align="char" valign="top" char="." charoff="50">0.56, 169.48</td><td align="char" valign="top" char="." charoff="50">0.12</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Females</italic></td></tr><tr><td align="left" valign="top" charoff="50"> AA</td><td align="char" valign="top" char="." charoff="50">8528</td><td align="char" valign="top" char="." charoff="50">8259</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> AG</td><td align="char" valign="top" char="." charoff="50">54</td><td align="char" valign="top" char="." charoff="50">45</td><td align="char" valign="top" char="." charoff="50">1.16</td><td align="char" valign="top" char="." charoff="50">0.78, 1.73</td><td align="char" valign="top" char="." charoff="50">0.46</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> GG</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">1.45</td><td align="char" valign="top" char="." charoff="50">0.24, 8.70</td><td align="char" valign="top" char="." charoff="50">0.68</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Genotype</italic><xref ref-type="fn" rid="t2-fn7">e</xref></td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Whole sample</italic></td></tr><tr><td align="left" valign="top" charoff="50"> WW</td><td align="char" valign="top" char="." charoff="50">19 767</td><td align="char" valign="top" char="." charoff="50">14 723</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> WM</td><td align="char" valign="top" char="." charoff="50">418</td><td align="char" valign="top" char="." charoff="50">280</td><td align="char" valign="top" char="." charoff="50">1.11</td><td align="char" valign="top" char="." charoff="50">0.95, 1.29</td><td align="char" valign="top" char="." charoff="50">0.17</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> MM</td><td align="char" valign="top" char="." charoff="50">76</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">28.30</td><td align="char" valign="top" char="." charoff="50">6.95, 115.26</td><td align="char" valign="top" char="." charoff="50">3.1 × 10<sup>−6</sup></td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> G396D AA</td><td align="char" valign="top" char="." charoff="50">31</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">23.09</td><td align="char" valign="top" char="." charoff="50">3.15, 169.15</td><td align="char" valign="top" char="." charoff="50">0.002</td><td align="char" valign="top" char="." charoff="50">46.93</td><td align="char" valign="top" char="." charoff="50">2.87, 766.89</td><td align="char" valign="top" char="." charoff="50">0.007</td></tr><tr><td align="left" valign="top" charoff="50"> Y179C GG</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">4.10</td><td align="char" valign="top" char="." charoff="50">0.91, 18.48</td><td align="char" valign="top" char="." charoff="50">0.07</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Compound heterozygous<xref ref-type="fn" rid="t2-fn8">f</xref></td><td align="char" valign="top" char="." charoff="50">29</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">21.60</td><td align="char" valign="top" char="." charoff="50">2.94, 158.58</td><td align="char" valign="top" char="." charoff="50">0.003</td><td align="char" valign="top" char="." charoff="50">43.95</td><td align="char" valign="top" char="." charoff="50">2.69, 719.26</td><td align="char" valign="top" char="." charoff="50">0.008</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ⩽<italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> WW</td><td align="char" valign="top" char="." charoff="50">6269</td><td align="char" valign="top" char="." charoff="50">5270</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> WM</td><td align="char" valign="top" char="." charoff="50">124</td><td align="char" valign="top" char="." charoff="50">104</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50">0.77, 1.30</td><td align="char" valign="top" char="." charoff="50">0.99</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> MM</td><td align="char" valign="top" char="." charoff="50">43</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">36.15</td><td align="char" valign="top" char="." charoff="50">4.98, 262.57</td><td align="char" valign="top" char="." charoff="50">0.0004</td><td align="char" valign="top" char="." charoff="50">73.14</td><td align="char" valign="top" char="." charoff="50">4.50, 1188.3</td><td align="char" valign="top" char="." charoff="50">0.003</td></tr><tr><td align="left" valign="top" charoff="50"> G396D AA</td><td align="char" valign="top" char="." charoff="50">13</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">10.93</td><td align="char" valign="top" char="." charoff="50">1.43, 83.57</td><td align="char" valign="top" char="." charoff="50">0.02</td><td align="char" valign="top" char="." charoff="50">22.70</td><td align="char" valign="top" char="." charoff="50">1.35, 381.91</td><td align="char" valign="top" char="." charoff="50">0.03</td></tr><tr><td align="left" valign="top" charoff="50"> Y179C GG</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">7.57</td><td align="char" valign="top" char="." charoff="50">0.96, 59.74</td><td align="char" valign="top" char="." charoff="50">0.06</td><td align="char" valign="top" char="." charoff="50">15.97</td><td align="char" valign="top" char="." charoff="50">0.93, 274.49</td><td align="char" valign="top" char="." charoff="50">0.06</td></tr><tr><td align="left" valign="top" charoff="50"> Compound heterozygous</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">14.29</td><td align="char" valign="top" char="." charoff="50">1.90, 107.42</td><td align="char" valign="top" char="." charoff="50">0.01</td><td align="char" valign="top" char="." charoff="50">29.42</td><td align="char" valign="top" char="." charoff="50">1.77, 489.38</td><td align="char" valign="top" char="." charoff="50">0.02</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> ><italic>55 Years old</italic></td></tr><tr><td align="left" valign="top" charoff="50"> WW</td><td align="char" valign="top" char="." charoff="50">13 498</td><td align="char" valign="top" char="." charoff="50">9453</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> WM</td><td align="char" valign="top" char="." charoff="50">294</td><td align="char" valign="top" char="." charoff="50">176</td><td align="char" valign="top" char="." charoff="50">1.17</td><td align="char" valign="top" char="." charoff="50">0.97, 1.41</td><td align="char" valign="top" char="." charoff="50">0.10</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> MM</td><td align="char" valign="top" char="." charoff="50">33</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">11.56</td><td align="char" valign="top" char="." charoff="50">2.77, 48.17</td><td align="char" valign="top" char="." charoff="50">0.001</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> G396D AA</td><td align="char" valign="top" char="." charoff="50">18</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">12.60</td><td align="char" valign="top" char="." charoff="50">1.68, 94.37</td><td align="char" valign="top" char="." charoff="50">0.01</td><td align="char" valign="top" char="." charoff="50">25.91</td><td align="char" valign="top" char="." charoff="50">1.56, 430.03</td><td align="char" valign="top" char="." charoff="50">0.02</td></tr><tr><td align="left" valign="top" charoff="50"> Y179C GG</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0.70</td><td align="char" valign="top" char="." charoff="50">0.10, 4.97</td><td align="char" valign="top" char="." charoff="50">0.72</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Compound heterozygous</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">8.40</td><td align="char" valign="top" char="." charoff="50">1.09, 64.64</td><td align="char" valign="top" char="." charoff="50">0.04</td><td align="char" valign="top" char="." charoff="50">17.51</td><td align="char" valign="top" char="." charoff="50">1.04, 295.75</td><td align="char" valign="top" char="." charoff="50">0.05</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Males</italic></td></tr><tr><td align="left" valign="top" charoff="50"> WW</td><td align="char" valign="top" char="." charoff="50">11 229</td><td align="char" valign="top" char="." charoff="50">6460</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> WM</td><td align="char" valign="top" char="." charoff="50">232</td><td align="char" valign="top" char="." charoff="50">119</td><td align="char" valign="top" char="." charoff="50">1.12</td><td align="char" valign="top" char="." charoff="50">0.90, 1.40</td><td align="char" valign="top" char="." charoff="50">0.31</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> MM</td><td align="char" valign="top" char="." charoff="50">36</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">20.71</td><td align="char" valign="top" char="." charoff="50">2.84, 151.09</td><td align="char" valign="top" char="." charoff="50">0.003</td><td align="char" valign="top" char="." charoff="50">42.00</td><td align="char" valign="top" char="." charoff="50">2.58, 684.38</td><td align="char" valign="top" char="." charoff="50">0.009</td></tr><tr><td align="left" valign="top" charoff="50"> G396D AA</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">8.62</td><td align="char" valign="top" char="." charoff="50">1.14, 65.25</td><td align="char" valign="top" char="." charoff="50">0.04</td><td align="char" valign="top" char="." charoff="50">17.84</td><td align="char" valign="top" char="." charoff="50">1.07, 298.11</td><td align="char" valign="top" char="." charoff="50">0.04</td></tr><tr><td align="left" valign="top" charoff="50"> Y179C GG</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">4.60</td><td align="char" valign="top" char="." charoff="50">0.58, 36.80</td><td align="char" valign="top" char="." charoff="50">0.15</td><td align="char" valign="top" char="." charoff="50">9.78</td><td align="char" valign="top" char="." charoff="50">0.56, 169.48</td><td align="char" valign="top" char="." charoff="50">0.12</td></tr><tr><td align="left" valign="top" charoff="50"> Compound heterozygous</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">6.90</td><td align="char" valign="top" char="." charoff="50">0.90, 53.10</td><td align="char" valign="top" char="." charoff="50">0.06</td><td align="char" valign="top" char="." charoff="50">14.38</td><td align="char" valign="top" char="." charoff="50">0.85, 242.96</td><td align="char" valign="top" char="." charoff="50">0.06</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"> <italic>Females</italic></td></tr><tr><td align="left" valign="top" charoff="50"> WW</td><td align="char" valign="top" char="." charoff="50">8528</td><td align="char" valign="top" char="." charoff="50">8259</td><td align="char" valign="top" char="." charoff="50">1.00</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> WM</td><td align="char" valign="top" char="." charoff="50">186</td><td align="char" valign="top" char="." charoff="50">161</td><td align="char" valign="top" char="." charoff="50">1.12</td><td align="char" valign="top" char="." charoff="50">0.90, 1.38</td><td align="char" valign="top" char="." charoff="50">0.30</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> MM</td><td align="char" valign="top" char="." charoff="50">40</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">19.37</td><td align="char" valign="top" char="." charoff="50">4.68, 80.17</td><td align="char" valign="top" char="." charoff="50">4.3 × 10<sup>−5</sup></td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> G396D AA</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">15.49</td><td align="char" valign="top" char="." charoff="50">2.05, 116.86</td><td align="char" valign="top" char="." charoff="50">0.008</td><td align="char" valign="top" char="." charoff="50">31.96</td><td align="char" valign="top" char="." charoff="50">1.92, 532.72</td><td align="char" valign="top" char="." charoff="50">0.02</td></tr><tr><td align="left" valign="top" charoff="50"> Y179C GG</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">1.45</td><td align="char" valign="top" char="." charoff="50">0.24, 8.70</td><td align="char" valign="top" char="." charoff="50">0.68</td><td align="char" valign="top" char="." charoff="50">NA</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td></tr><tr><td align="left" valign="top" charoff="50"> Compound heterozygous</td><td align="char" valign="top" char="." charoff="50">17</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">16.46</td><td align="char" valign="top" char="." charoff="50">2.19, 123.70</td><td align="char" valign="top" char="." charoff="50">0.006</td><td align="char" valign="top" char="." charoff="50">33.90</td><td align="char" valign="top" char="." charoff="50">2.04, 563.74</td><td align="char" valign="top" char="." charoff="50">0.01</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Abbreviations: CI=confidence interval; MM=mutated/mutated; NA=not available; OR=odds ratio; WM=wild type/mutant; WW=wild type/wild type.</p></fn><fn id="t2-fn2"><p><sup>*</sup>Crude analysis.</p></fn><fn id="t2-fn3"><label>a</label><p>Estimated by adding one control with the variant genotype.</p></fn><fn id="t2-fn4"><label>b</label><p>Estimated using the meta command of STATA and for mathematical reasons, cells with zero frequencies were assumed to be 0.5 (as defaulted by the meta command).</p></fn><fn id="t2-fn5"><label>c</label><p>Analysis conducted only for the AA Y179C, that is, WW.</p></fn><fn id="t2-fn6"><label>d</label><p>Analysis conducted only for the GG G396D, that is, WW.</p></fn><fn id="t2-fn7"><label>e</label><p>Including subjects with data for both Y179C and G396D.</p></fn><fn id="t2-fn8"><label>f</label><p>This category includes 29 G396D GA and Y179C AG cases; 5 cases with either G396D GA or Y179C AG and any other pathogenic <italic>MUTYH</italic> mutation were excluded.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl3"><label>Table 3</label><caption><title>Meta-analysis of studies<xref ref-type="fn" rid="t3-fn2">a</xref></title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Genotype (cases)</bold></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Genotype (controls)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>WM <italic>vs</italic> WW</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>MM <italic>vs</italic> WW</bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Study</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WW</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WM</bold></th><th align="center" valign="top" char="." charoff="50"><bold>MM</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WW</bold></th><th align="center" valign="top" char="." charoff="50"><bold>WM</bold></th><th align="center" valign="top" char="." charoff="50"><bold>MM</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib9">Enholm <italic>et al</italic> (2003)</xref></td><td align="char" valign="top" char="." charoff="50">994</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">424</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">4.70 (0.26, 85.10)</td><td align="char" valign="top" char="(" charoff="50">3.84 (0.21, 71.51)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib16">Kambara <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">90</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">52</td><td align="char" valign="top" char="." charoff="50">—</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.16 (0.10, 13.06)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib28">Wang <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">10</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">309</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.79 (0.56, 5.75)</td><td align="char" valign="top" char="(" charoff="50">3.58 (0.17, 74.79)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib30">Zhou <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">466</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">2.16 (0.54, 8.68)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib22">Peterlongo <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">549</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">911</td><td align="char" valign="top" char="." charoff="50">7</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.95 (0.28, 3.25)</td><td align="char" valign="top" char="(" charoff="50">8.29 (0.40, 173.08)</td></tr><tr><td align="left" valign="top" charoff="50">Tomlinson I (2006)<xref ref-type="fn" rid="t3-fn3">b</xref></td><td align="char" valign="top" char="." charoff="50">662</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">197</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">2.23 (0.51, 9.84)</td><td align="char" valign="top" char="(" charoff="50">0.89 (0.04, 22.04)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib19">Moreno <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">323</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">278</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.29 (0.45, 3.67)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib6">Colebatch <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">859</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">473</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.21 (0.42, 3.51)</td><td align="char" valign="top" char="(" charoff="50">2.75 (0.13, 57.49)</td></tr><tr><td align="left" valign="top" charoff="50">Koessler T (2007)<xref ref-type="fn" rid="t3-fn4">c</xref></td><td align="char" valign="top" char="." charoff="50">2198</td><td align="char" valign="top" char="." charoff="50">37</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">2204</td><td align="char" valign="top" char="." charoff="50">42</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.88 (0.57, 1.38)</td><td align="char" valign="top" char="(" charoff="50">19.05 (1.11, 327.53)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib17">Küry <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">999</td><td align="char" valign="top" char="." charoff="50">24</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">1100</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.26 (0.70, 2.27)</td><td align="char" valign="top" char="(" charoff="50">3.30 (0.13, 81.18)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib3">Balaguer <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">1089</td><td align="char" valign="top" char="." charoff="50">19</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">912</td><td align="char" valign="top" char="." charoff="50">22</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.72 (0.39, 1.34)</td><td align="char" valign="top" char="(" charoff="50">14.24 (0.82, 247.02)</td></tr><tr><td align="left" valign="top" charoff="50">SOCCS (2008)<xref ref-type="fn" rid="t3-fn5">d</xref></td><td align="char" valign="top" char="." charoff="50">3429</td><td align="char" valign="top" char="." charoff="50">77</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">2993</td><td align="char" valign="top" char="." charoff="50">57</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.18 (0.83, 1.67)</td><td align="char" valign="top" char="(" charoff="50">28.80 (1.73, 480.32)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib2">Avezzù <italic>et al</italic> (2008)</xref></td><td align="char" valign="top" char="." charoff="50">435</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">246</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.13 (0.10, 12.54)</td><td align="char" valign="top" char="(" charoff="50">2.83 (0.14, 59.19)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib5">Cleary <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t3-fn6">e</xref></td><td align="char" valign="top" char="." charoff="50">3697</td><td align="char" valign="top" char="." charoff="50">87</td><td align="char" valign="top" char="." charoff="50">27</td><td align="char" valign="top" char="." charoff="50">2758</td><td align="char" valign="top" char="." charoff="50">43</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1.51 (1.04, 2.18)</td><td align="char" valign="top" char="(" charoff="50">20.14 (2.74, 148.32)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib18">Lubbe <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t3-fn7">f</xref></td><td align="char" valign="top" char="." charoff="50">9043</td><td align="char" valign="top" char="." charoff="50">198</td><td align="char" valign="top" char="." charoff="50">27</td><td align="char" valign="top" char="." charoff="50">4962</td><td align="char" valign="top" char="." charoff="50">101</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1.08 (0.84, 1.37)</td><td align="char" valign="top" char="(" charoff="50">14.82 (2.01, 109.06)</td></tr><tr><td align="left" valign="top" charoff="50"><italic>M–H pooled effect (fixed)</italic></td><td align="char" valign="top" char="." charoff="50">25231</td><td align="char" valign="top" char="." charoff="50">506</td><td align="char" valign="top" char="." charoff="50">101</td><td align="char" valign="top" char="." charoff="50">18285</td><td align="char" valign="top" char="." charoff="50">315</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="(" charoff="50">1.16 (1.00, 1.34)</td><td align="char" valign="top" char="(" charoff="50">10.80 (5.02, 23.21)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.05</td><td align="char" valign="top" char="(" charoff="50"><0.0005</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Heterogeneity</italic></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.82</td><td align="char" valign="top" char="(" charoff="50">0.84</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>I</italic><sup>2</sup> (95% CI)</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0 (0, 54)</td><td align="char" valign="top" char="(" charoff="50">0 (0, 60)</td></tr></tbody></table><table-wrap-foot><fn id="t3-fn1"><p>Abbreviations: CI=confidence interval; MM=mutated/mutated; NA=not available; OR=odds ratio; WM=wild type/mutant; WW=wild type/wild type.</p></fn><fn id="t3-fn2"><label>a</label><p>This table presents the data as they were published. Two unpublished studies included.</p></fn><fn id="t3-fn3"><label>b</label><p>Unpublished data obtained in 2006.</p></fn><fn id="t3-fn4"><label>c</label><p>Unpublished data obtained in 2007.</p></fn><fn id="t3-fn5"><label>d</label><p>Includes data from <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006)</xref> and unpublished data from the SOCCS study obtained in 2008.</p></fn><fn id="t3-fn6"><label>e</label><p>Includes data from <xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref>.</p></fn><fn id="t3-fn7"><label>f</label><p>Includes data from <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl4"><label>Table 4</label><caption><title>Meta-analysis of studies for the G396D genotypes<xref ref-type="fn" rid="t4-fn2">a</xref></title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>G396D (cases)</bold></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>G396D (controls)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>GA <italic>vs</italic> GG</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>AA <italic>vs</italic> GG</bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Study</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib9">Enholm <italic>et al</italic> (2003)</xref></td><td align="char" valign="top" char="." charoff="50">994</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">424</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">3.84 (0.21, 71.51)</td><td align="char" valign="top" char="(" charoff="50">1.28 (0.05, 31.50)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib16">Kambara <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">90</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">52</td><td align="char" valign="top" char="." charoff="50">—</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">Not enough data available</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib28">Wang <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">309</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.79 (0.35, 9.28)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib30">Zhou <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">466</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.08 (0.07, 17.30)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib22">Peterlongo <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">549</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">911</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.66 (0.13, 3.43)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50">Tomlinson I (2006)<xref ref-type="fn" rid="t4-fn3">b</xref></td><td align="char" valign="top" char="." charoff="50">662</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">197</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.34 (0.29, 6.25)</td><td align="char" valign="top" char="(" charoff="50">0.89 (0.04, 22.04)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib19">Moreno <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">323</td><td align="char" valign="top" char="." charoff="50">9</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">278</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.29 (0.45, 3.67)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib6">Colebatch <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">859</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">473</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.10 (0.33, 3.67)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50">Koessler T (2007)<xref ref-type="fn" rid="t4-fn4">c</xref></td><td align="char" valign="top" char="." charoff="50">2198</td><td align="char" valign="top" char="." charoff="50">25</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">2204</td><td align="char" valign="top" char="." charoff="50">31</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.81 (0.48, 1.37)</td><td align="char" valign="top" char="(" charoff="50">5.01 (0.24, 104.49)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib17">Küry <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">999</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1100</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.45 (0.75, 2.79)</td><td align="char" valign="top" char="(" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib3">Balaguer <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">1089</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">912</td><td align="char" valign="top" char="." charoff="50">20</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.63 (0.32, 1.23)</td><td align="char" valign="top" char="(" charoff="50">2.51 (0.10, 61.75)</td></tr><tr><td align="left" valign="top" charoff="50">SOCCS (2008)<xref ref-type="fn" rid="t4-fn5">d</xref></td><td align="char" valign="top" char="." charoff="50">3429</td><td align="char" valign="top" char="." charoff="50">56</td><td align="char" valign="top" char="." charoff="50">8</td><td align="char" valign="top" char="." charoff="50">2993</td><td align="char" valign="top" char="." charoff="50">42</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.16 (0.78, 1.74)</td><td align="char" valign="top" char="(" charoff="50">14.84 (0.86, 257.19)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib2">Avezzù <italic>et al</italic> (2008)</xref></td><td align="char" valign="top" char="." charoff="50">435</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">246</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">2.83 (0.14, 59.19)</td><td align="char" valign="top" char="(" charoff="50">1.70 (0.07, 41.84)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib5">Cleary <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t4-fn6">e</xref></td><td align="char" valign="top" char="." charoff="50">3697</td><td align="char" valign="top" char="." charoff="50">63</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">2758</td><td align="char" valign="top" char="." charoff="50">32</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.47 (0.96, 2.25)</td><td align="char" valign="top" char="(" charoff="50">17.16 (1.01, 291.31)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib18">Lubbe <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t4-fn7">f</xref></td><td align="char" valign="top" char="." charoff="50">9043</td><td align="char" valign="top" char="." charoff="50">128</td><td align="char" valign="top" char="." charoff="50">10</td><td align="char" valign="top" char="." charoff="50">4962</td><td align="char" valign="top" char="." charoff="50">75</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.94 (0.70, 1.25)</td><td align="char" valign="top" char="(" charoff="50">11.52 (0.68, 196.69)</td></tr><tr><td align="left" valign="top" charoff="50"><italic>M–H pooled effect (fixed)</italic></td><td align="char" valign="top" char="." charoff="50">25 231</td><td align="char" valign="top" char="." charoff="50">350</td><td align="char" valign="top" char="." charoff="50">35</td><td align="char" valign="top" char="." charoff="50">18 285</td><td align="char" valign="top" char="." charoff="50">236</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.07 (0.90, 1.26)</td><td align="char" valign="top" char="(" charoff="50">6.47 (2.33, 17.97)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.44</td><td align="char" valign="top" char="(" charoff="50"><0.0005</td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Heterogeneity</italic></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.74</td><td align="char" valign="top" char="(" charoff="50">0.73</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>I</italic><sup>2</sup> (95% CI)</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0 (0, 55)</td><td align="char" valign="top" char="(" charoff="50">0 (0, 68)</td></tr></tbody></table><table-wrap-foot><fn id="t4-fn1"><p>Abbreviations: CI=confidence interval; MM=mutated/mutated; NA=not available; OR=odds ratio; WM=wild type/mutant; WW=wild type/wild type.</p></fn><fn id="t4-fn2"><label>a</label><p>This table presents the data as they were published. Two unpublished studies included.</p></fn><fn id="t4-fn3"><label>b</label><p>Unpublished data obtained in 2006.</p></fn><fn id="t4-fn4"><label>c</label><p>Unpublished data obtained in 2007.</p></fn><fn id="t4-fn5"><label>d</label><p>Includes data from <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006)</xref> and unpublished data from the SOCCS study obtained in 2008.</p></fn><fn id="t4-fn6"><label>e</label><p>Includes data from <xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref>.</p></fn><fn id="t4-fn7"><label>f</label><p>Includes data from <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl5"><label>Table 5</label><caption><title>Meta-analysis of studies for the Y179C genotypes<xref ref-type="fn" rid="t5-fn2">a</xref></title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="."></col><col align="char" char="("></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Y179C (cases)</bold></th><th colspan="3" align="center" valign="top" char="." charoff="50"><bold>Y179C (controls)</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>AG <italic>vs</italic> AA</bold></th><th align="center" valign="top" charoff="50"><bold>GG <italic>vs</italic> AA</bold></th></tr><tr><th align="left" valign="top" charoff="50"><bold>Study</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AA</bold></th><th align="center" valign="top" char="." charoff="50"><bold>AG</bold></th><th align="center" valign="top" char="." charoff="50"><bold>GG</bold></th><th align="center" valign="top" char="(" charoff="50"><bold>OR (95% CI)</bold></th><th align="center" valign="top" charoff="50"><bold>OR (95% CI)</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib9">Enholm <italic>et al</italic> (2003)</xref></td><td align="char" valign="top" char="." charoff="50">994</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">424</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.28 (0.05, 31.50)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib16">Kambara <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">90</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">52</td><td align="char" valign="top" char="." charoff="50">—</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">Not enough data available</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib28">Wang <italic>et al</italic> (2004)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">309</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.79 (0.35, 9.28)</td><td align="left" valign="top" charoff="50">2.15 (0.09, 52.87)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib30">Zhou <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">432</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">466</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.62 (0.35, 9.28)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib22">Peterlongo <italic>et al</italic> (2005)</xref></td><td align="char" valign="top" char="." charoff="50">549</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">911</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.66 (0.23, 11.81)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50">Tomlinson I (2006)<xref ref-type="fn" rid="t5-fn3">b</xref></td><td align="char" valign="top" char="." charoff="50">662</td><td align="char" valign="top" char="." charoff="50">6</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">197</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">3.88 (0.22, 69.10)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib19">Moreno <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">323</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">278</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">NA</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib6">Colebatch <italic>et al</italic> (2006)</xref></td><td align="char" valign="top" char="." charoff="50">859</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">473</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.65 (0.17, 15.93)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50">Koessler T (2007)<xref ref-type="fn" rid="t5-fn4">c</xref></td><td align="char" valign="top" char="." charoff="50">2198</td><td align="char" valign="top" char="." charoff="50">12</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">2204</td><td align="char" valign="top" char="." charoff="50">11</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.09 (0.48, 2.48)</td><td align="left" valign="top" charoff="50">3.01 (0.12, 73.88)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib17">Küry <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">999</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">1100</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.83 (0.18, 3.70)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib3">Balaguer <italic>et al</italic> (2007)</xref></td><td align="char" valign="top" char="." charoff="50">1089</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="." charoff="50">912</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">3.35 (0.37, 30.02)</td><td align="left" valign="top" charoff="50">4.19 (0.20, 87.34)</td></tr><tr><td align="left" valign="top" charoff="50">SOCCS (2008)<xref ref-type="fn" rid="t5-fn5">d</xref></td><td align="char" valign="top" char="." charoff="50">3429</td><td align="char" valign="top" char="." charoff="50">21</td><td align="char" valign="top" char="." charoff="50">3</td><td align="char" valign="top" char="." charoff="50">2993</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">1.22 (0.63, 2.38)</td><td align="left" valign="top" charoff="50">6.11 (0.32, 118.34)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib2">Avezzù <italic>et al</italic> (2008)</xref></td><td align="char" valign="top" char="." charoff="50">435</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="." charoff="50">246</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="." charoff="50">0</td><td align="char" valign="top" char="(" charoff="50">0.19 (0.01, 4.65)</td><td align="left" valign="top" charoff="50">NA</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib5">Cleary <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t5-fn6">e</xref></td><td align="char" valign="top" char="." charoff="50">3697</td><td align="char" valign="top" char="." charoff="50">15</td><td align="char" valign="top" char="." charoff="50">5</td><td align="char" valign="top" char="." charoff="50">2758</td><td align="char" valign="top" char="." charoff="50">10</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1.12 (0.50, 2.50)</td><td align="left" valign="top" charoff="50">3.73 (0.44, 31.95)</td></tr><tr><td align="left" valign="top" charoff="50"><xref ref-type="bibr" rid="bib18">Lubbe <italic>et al</italic> (2009)</xref><xref ref-type="fn" rid="t5-fn7">f</xref></td><td align="char" valign="top" char="." charoff="50">9043</td><td align="char" valign="top" char="." charoff="50">70</td><td align="char" valign="top" char="." charoff="50">4</td><td align="char" valign="top" char="." charoff="50">4962</td><td align="char" valign="top" char="." charoff="50">26</td><td align="char" valign="top" char="." charoff="50">1</td><td align="char" valign="top" char="(" charoff="50">1.48 (0.94, 2.32)</td><td align="left" valign="top" charoff="50">2.20 (0.25, 19.64)</td></tr><tr><td align="left" valign="top" charoff="50"><italic>M-H pooled effect (fixed)</italic></td><td align="char" valign="top" char="." charoff="50">25 231</td><td align="char" valign="top" char="." charoff="50">145</td><td align="char" valign="top" char="." charoff="50">16</td><td align="char" valign="top" char="." charoff="50">18 285</td><td align="char" valign="top" char="." charoff="50">75</td><td align="char" valign="top" char="." charoff="50">2</td><td align="char" valign="top" char="(" charoff="50">1.34 (1.01, 1.77)</td><td align="left" valign="top" charoff="50">3.35 (1.14, 9.89)</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.04</td><td align="left" valign="top" charoff="50">0.03</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50"> </td><td align="left" valign="top" charoff="50"> </td></tr><tr><td colspan="9" align="left" valign="top" charoff="50"><italic>Heterogeneity</italic></td></tr><tr><td align="left" valign="top" charoff="50"> <italic>P</italic>-value</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0.98</td><td align="left" valign="top" charoff="50">0.99</td></tr><tr><td align="left" valign="top" charoff="50"> <italic>I</italic><sup>2</sup> (95% CI)</td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="." charoff="50"> </td><td align="char" valign="top" char="(" charoff="50">0 (0, 57)</td><td align="left" valign="top" charoff="50">0 (0, 75)</td></tr></tbody></table><table-wrap-foot><fn id="t5-fn1"><p>Abbreviations: CI=confidence interval; MM=mutated/mutated; NA=not available; OR=odds ratio; WM=wild type/mutant; WW=wild type/wild type.</p></fn><fn id="t5-fn2"><label>a</label><p>This table presents the data as they were published. Two unpublished studies included.</p></fn><fn id="t5-fn3"><label>b</label><p>Unpublished data obtained in 2006.</p></fn><fn id="t5-fn4"><label>c</label><p>Unpublished data obtained in 2007.</p></fn><fn id="t5-fn5"><label>d</label><p>Includes data from <xref ref-type="bibr" rid="bib10">Farrington <italic>et al</italic> (2005)</xref>, <xref ref-type="bibr" rid="bib25">Tenesa <italic>et al</italic> (2006)</xref> and unpublished data from the SOCCS study obtained in 2008.</p></fn><fn id="t5-fn6"><label>e</label><p>Includes data from <xref ref-type="bibr" rid="bib7">Croitoru <italic>et al</italic> (2004)</xref>.</p></fn><fn id="t5-fn7"><label>f</label><p>Includes data from <xref ref-type="bibr" rid="bib29">Webb <italic>et al</italic> (2006)</xref> and <xref ref-type="bibr" rid="bib12">Fleischmann <italic>et al</italic> (2004)</xref>.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Australie</li><li>Canada</li><li>Espagne</li><li>Finlande</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>Suède</li><li>États-Unis</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Theodoratou, E" sort="Theodoratou, E" uniqKey="Theodoratou E" first="E" last="Theodoratou">E. Theodoratou</name></noRegion><name sortKey="Barnetson, R" sort="Barnetson, R" uniqKey="Barnetson R" first="R" last="Barnetson">R. Barnetson</name><name sortKey="Broderick, P" sort="Broderick, P" uniqKey="Broderick P" first="P" last="Broderick">P. Broderick</name><name sortKey="Campbell, H" sort="Campbell, H" uniqKey="Campbell H" first="H" last="Campbell">H. Campbell</name><name sortKey="Campbell, H" sort="Campbell, H" uniqKey="Campbell H" first="H" last="Campbell">H. Campbell</name><name sortKey="Dunlop, M G" sort="Dunlop, M G" uniqKey="Dunlop M" first="M G" last="Dunlop">M G Dunlop</name><name sortKey="Farrington, S M" sort="Farrington, S M" uniqKey="Farrington S" first="S M" last="Farrington">S M Farrington</name><name sortKey="Houlston, R" sort="Houlston, R" uniqKey="Houlston R" first="R" last="Houlston">R. Houlston</name><name sortKey="Koessler, T" sort="Koessler, T" uniqKey="Koessler T" first="T" last="Koessler">T. Koessler</name><name sortKey="Lubbe, S" sort="Lubbe, S" uniqKey="Lubbe S" first="S" last="Lubbe">S. Lubbe</name><name sortKey="Pharoah, P D" sort="Pharoah, P D" uniqKey="Pharoah P" first="P D" last="Pharoah">P D Pharoah</name><name sortKey="Porteous, M E" sort="Porteous, M E" uniqKey="Porteous M" first="M E" last="Porteous">M E Porteous</name><name sortKey="Porteous, M E" sort="Porteous, M E" uniqKey="Porteous M" first="M E" last="Porteous">M E Porteous</name><name sortKey="Tenesa, A" sort="Tenesa, A" uniqKey="Tenesa A" first="A" last="Tenesa">A. Tenesa</name><name sortKey="Theodoratou, E" sort="Theodoratou, E" uniqKey="Theodoratou E" first="E" last="Theodoratou">E. Theodoratou</name><name sortKey="Tomlinson, I P" sort="Tomlinson, I P" uniqKey="Tomlinson I" first="I P" last="Tomlinson">I P Tomlinson</name><name sortKey="Webb, E" sort="Webb, E" uniqKey="Webb E" first="E" last="Webb">E. Webb</name></country><country name="Canada"><noRegion><name sortKey="Gallinger, S" sort="Gallinger, S" uniqKey="Gallinger S" first="S" last="Gallinger">S. Gallinger</name></noRegion><name sortKey="Cleary, S P" sort="Cleary, S P" uniqKey="Cleary S" first="S P" last="Cleary">S P Cleary</name><name sortKey="Croitoru, E M" sort="Croitoru, E M" uniqKey="Croitoru E" first="E M" last="Croitoru">E M Croitoru</name></country><country name="Australie"><noRegion><name sortKey="Jenkins, M A" sort="Jenkins, M A" uniqKey="Jenkins M" first="M A" last="Jenkins">M A Jenkins</name></noRegion><name sortKey="Win, A K" sort="Win, A K" uniqKey="Win A" first="A K" last="Win">A K Win</name></country><country name="France"><noRegion><name sortKey="Kury, S" sort="Kury, S" uniqKey="Kury S" first="S" last="Küry">S. Küry</name></noRegion><name sortKey="Bezieau, S" sort="Bezieau, S" uniqKey="Bezieau S" first="S" last="Bézieau">S. Bézieau</name><name sortKey="Buecher, B" sort="Buecher, B" uniqKey="Buecher B" first="B" last="Buecher">B. Buecher</name></country><country name="États-Unis"><noRegion><name sortKey="Ellis, N A" sort="Ellis, N A" uniqKey="Ellis N" first="N A" last="Ellis">N A Ellis</name></noRegion><name sortKey="Offit, K" sort="Offit, K" uniqKey="Offit K" first="K" last="Offit">K. Offit</name></country><country name="Italie"><noRegion><name sortKey="Peterlongo, P" sort="Peterlongo, P" uniqKey="Peterlongo P" first="P" last="Peterlongo">P. Peterlongo</name></noRegion></country><country name="Finlande"><noRegion><name sortKey="Aaltonen, L A" sort="Aaltonen, L A" uniqKey="Aaltonen L" first="L A" last="Aaltonen">L A Aaltonen</name></noRegion><name sortKey="Enholm, S" sort="Enholm, S" uniqKey="Enholm S" first="S" last="Enholm">S. Enholm</name></country><country name="Suède"><noRegion><name sortKey="Lindblom, A" sort="Lindblom, A" uniqKey="Lindblom A" first="A" last="Lindblom">A. Lindblom</name></noRegion><name sortKey="Zhou, X L" sort="Zhou, X L" uniqKey="Zhou X" first="X-L" last="Zhou">X-L Zhou</name></country><country name="Espagne"><noRegion><name sortKey="Moreno, V" sort="Moreno, V" uniqKey="Moreno V" first="V" last="Moreno">V. Moreno</name></noRegion><name sortKey="Blanco, I" sort="Blanco, I" uniqKey="Blanco I" first="I" last="Blanco">I. Blanco</name><name sortKey="Capella, G" sort="Capella, G" uniqKey="Capella G" first="G" last="Capellà">G. Capellà</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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