Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer
Identifieur interne : 005374 ( Main/Exploration ); précédent : 005373; suivant : 005375Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer
Auteurs : Shuo Jiao [États-Unis] ; Li Hsu [États-Unis] ; Sonja Berndt [États-Unis] ; Stéphane Bézieau [France] ; Hermann Brenner [Allemagne] ; Daniel Buchanan [Australie] ; Bette J. Caan [États-Unis] ; Peter T. Campbell [États-Unis] ; Christopher S. Carlson [États-Unis] ; Graham Casey [États-Unis] ; Andrew T. Chan [États-Unis] ; Jenny Chang-Claude [Allemagne] ; Stephen Chanock [États-Unis] ; David V. Conti [États-Unis] ; Keith R. Curtis [États-Unis] ; David Duggan [États-Unis] ; Steven Gallinger [Canada] ; Stephen B. Gruber [États-Unis] ; Tabitha A. Harrison [États-Unis] ; Richard B. Hayes [États-Unis] ; Brian E. Henderson [États-Unis] ; Michael Hoffmeister [Allemagne] ; John L. Hopper [Australie] ; Thomas J. Hudson [Canada] ; Carolyn M. Hutter [États-Unis] ; Rebecca D. Jackson [États-Unis] ; Mark A. Jenkins [Australie] ; Elizabeth D. Kantor [États-Unis] ; Laurence N. Kolonel [États-Unis] ; Sébastien Küry [France] ; Loic Le Marchand [États-Unis] ; Mathieu Lemire [Canada] ; Polly A. Newcomb [États-Unis] ; John D. Potter [États-Unis, Nouvelle-Zélande] ; Conghui Qu [États-Unis] ; Stephanie A. Rosse [États-Unis] ; Robert E. Schoen [États-Unis] ; Fred R. Schumacher [États-Unis] ; Daniela Seminara [États-Unis] ; Martha L. Slattery [États-Unis] ; Cornelia M. Ulrich [États-Unis, Allemagne] ; Brent W. Zanke [Canada] ; Ulrike Peters [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10−4). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×10−8. Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×10−6; Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.
Url:
DOI: 10.1371/journal.pone.0052535
PubMed: 23300701
PubMed Central: 3530500
Affiliations:
- Allemagne, Australie, Canada, France, Nouvelle-Zélande, États-Unis
- Arizona, Bade-Wurtemberg, Californie, District de Karlsruhe, Géorgie (États-Unis), Hawaï, Maryland, Massachusetts, Ohio, Ontario, Pays de la Loire, Pennsylvanie, Utah, Victoria (État), Washington (État), État de New York
- Heidelberg, Los Angeles, Melbourne, Nantes, Seattle, Toronto
- Université de Californie du Sud, Université de Melbourne, Université de Toronto, Université de Washington
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Gruber</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Harrison, Tabitha A" sort="Harrison, Tabitha A" uniqKey="Harrison T" first="Tabitha A." last="Harrison">Tabitha A. Harrison</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name><affiliation wicri:level="2"><nlm:aff id="aff15"><addr-line>Division of Epidemiology, New York University School of Medicine, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Epidemiology, New York University School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Henderson, Brian E" sort="Henderson, Brian E" uniqKey="Henderson B" first="Brian E." last="Henderson">Brian E. Henderson</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation wicri:level="4"><nlm:aff id="aff16"><addr-line>Melbourne School of Population Health, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne School of Population Health, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Ontario Institute for Cancer Research, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Ontario Institute for Cancer Research, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Jackson, Rebecca D" sort="Jackson, Rebecca D" uniqKey="Jackson R" first="Rebecca D." last="Jackson">Rebecca D. Jackson</name><affiliation wicri:level="2"><nlm:aff id="aff19"><addr-line>Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus, Ohio, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name><affiliation wicri:level="4"><nlm:aff id="aff16"><addr-line>Melbourne School of Population Health, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne School of Population Health, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Kantor, Elizabeth D" sort="Kantor, Elizabeth D" uniqKey="Kantor E" first="Elizabeth D." last="Kantor">Elizabeth D. Kantor</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Kolonel, Laurence N" sort="Kolonel, Laurence N" uniqKey="Kolonel L" first="Laurence N." last="Kolonel">Laurence N. Kolonel</name><affiliation wicri:level="2"><nlm:aff id="aff20"><addr-line>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</wicri:regionArea><placeName><region type="state">Hawaï</region></placeName></affiliation></author><author><name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Service de Génétique Médicale, CHU Nantes, Nantes, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, CHU Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name><affiliation wicri:level="2"><nlm:aff id="aff20"><addr-line>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</wicri:regionArea><placeName><region type="state">Hawaï</region></placeName></affiliation></author><author><name sortKey="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Ontario Institute for Cancer Research, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Ontario Institute for Cancer Research, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. 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Rosse</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name><affiliation wicri:level="2"><nlm:aff id="aff22"><addr-line>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Schumacher, Fred R" sort="Schumacher, Fred R" uniqKey="Schumacher F" first="Fred R." last="Schumacher">Fred R. 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Slattery</name><affiliation wicri:level="2"><nlm:aff id="aff24"><addr-line>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Zanke, Brent W" sort="Zanke, Brent W" uniqKey="Zanke B" first="Brent W." last="Zanke">Brent W. Zanke</name><affiliation wicri:level="1"><nlm:aff id="aff26"><addr-line>Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa</wicri:regionArea><wicri:noRegion>Ottawa</wicri:noRegion></affiliation></author><author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23300701</idno><idno type="pmc">3530500</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530500</idno><idno type="RBID">PMC:3530500</idno><idno type="doi">10.1371/journal.pone.0052535</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002A56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002A56</idno><idno type="wicri:Area/Pmc/Curation">002906</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002906</idno><idno type="wicri:Area/Pmc/Checkpoint">001F29</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001F29</idno><idno type="wicri:Area/Ncbi/Merge">001089</idno><idno type="wicri:Area/Ncbi/Curation">001089</idno><idno type="wicri:Area/Ncbi/Checkpoint">001089</idno><idno type="wicri:Area/Main/Merge">005613</idno><idno type="wicri:Area/Main/Curation">005374</idno><idno type="wicri:Area/Main/Exploration">005374</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer</title><author><name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Berndt, Sonja" sort="Berndt, Sonja" uniqKey="Berndt S" first="Sonja" last="Berndt">Sonja Berndt</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Service de Génétique Médicale, CHU Nantes, Nantes, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, CHU Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Buchanan, Daniel" sort="Buchanan, Daniel" uniqKey="Buchanan D" first="Daniel" last="Buchanan">Daniel Buchanan</name><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland</wicri:regionArea><wicri:noRegion>Queensland</wicri:noRegion></affiliation></author><author><name sortKey="Caan, Bette J" sort="Caan, Bette J" uniqKey="Caan B" first="Bette J." last="Caan">Bette J. Caan</name><affiliation wicri:level="2"><nlm:aff id="aff6"><addr-line>Division of Research, Kaiser Permanente Medical Care Program, Oakland, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Research, Kaiser Permanente Medical Care Program, Oakland, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Campbell, Peter T" sort="Campbell, Peter T" uniqKey="Campbell P" first="Peter T." last="Campbell">Peter T. Campbell</name><affiliation wicri:level="2"><nlm:aff id="aff7"><addr-line>Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Epidemiology Research Program, American Cancer Society, Atlanta, Georgia</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Carlson, Christopher S" sort="Carlson, Christopher S" uniqKey="Carlson C" first="Christopher S." last="Carlson">Christopher S. 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Chan</name><affiliation wicri:level="2"><nlm:aff id="aff10"><addr-line>Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="aff11"><addr-line>Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><affiliation wicri:level="3"><nlm:aff id="aff12"><addr-line>Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name><affiliation wicri:level="2"><nlm:aff id="aff2"><addr-line>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Curtis, Keith R" sort="Curtis, Keith R" uniqKey="Curtis K" first="Keith R." last="Curtis">Keith R. Curtis</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Duggan, David" sort="Duggan, David" uniqKey="Duggan D" first="David" last="Duggan">David Duggan</name><affiliation wicri:level="2"><nlm:aff id="aff13"><addr-line>Translational Genomics Research Institute, Phoenix, Arizona, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Translational Genomics Research Institute, Phoenix, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name><affiliation wicri:level="1"><nlm:aff id="aff14"><addr-line>Department of Surgery, University Health Network, Toronto General Hospital, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Surgery, University Health Network, Toronto General Hospital, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Gruber, Stephen B" sort="Gruber, Stephen B" uniqKey="Gruber S" first="Stephen B." last="Gruber">Stephen B. Gruber</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Harrison, Tabitha A" sort="Harrison, Tabitha A" uniqKey="Harrison T" first="Tabitha A." last="Harrison">Tabitha A. Harrison</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name><affiliation wicri:level="2"><nlm:aff id="aff15"><addr-line>Division of Epidemiology, New York University School of Medicine, New York, New York, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Epidemiology, New York University School of Medicine, New York, New York</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Henderson, Brian E" sort="Henderson, Brian E" uniqKey="Henderson B" first="Brian E." last="Henderson">Brian E. Henderson</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name><affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation wicri:level="4"><nlm:aff id="aff16"><addr-line>Melbourne School of Population Health, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne School of Population Health, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Ontario Institute for Cancer Research, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Ontario Institute for Cancer Research, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff18"><addr-line>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Jackson, Rebecca D" sort="Jackson, Rebecca D" uniqKey="Jackson R" first="Rebecca D." last="Jackson">Rebecca D. Jackson</name><affiliation wicri:level="2"><nlm:aff id="aff19"><addr-line>Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus, Ohio, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus, Ohio</wicri:regionArea><placeName><region type="state">Ohio</region></placeName></affiliation></author><author><name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name><affiliation wicri:level="4"><nlm:aff id="aff16"><addr-line>Melbourne School of Population Health, University of Melbourne, Melbourne, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne School of Population Health, University of Melbourne, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Kantor, Elizabeth D" sort="Kantor, Elizabeth D" uniqKey="Kantor E" first="Elizabeth D." last="Kantor">Elizabeth D. Kantor</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Kolonel, Laurence N" sort="Kolonel, Laurence N" uniqKey="Kolonel L" first="Laurence N." last="Kolonel">Laurence N. Kolonel</name><affiliation wicri:level="2"><nlm:aff id="aff20"><addr-line>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</wicri:regionArea><placeName><region type="state">Hawaï</region></placeName></affiliation></author><author><name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Service de Génétique Médicale, CHU Nantes, Nantes, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, CHU Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name><affiliation wicri:level="2"><nlm:aff id="aff20"><addr-line>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</wicri:regionArea><placeName><region type="state">Hawaï</region></placeName></affiliation></author><author><name sortKey="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name><affiliation wicri:level="1"><nlm:aff id="aff17"><addr-line>Ontario Institute for Cancer Research, Toronto, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Ontario Institute for Cancer Research, Toronto</wicri:regionArea><wicri:noRegion>Toronto</wicri:noRegion></affiliation></author><author><name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff21"><addr-line>Centre for Public Health Research, Massey University, Wellington, New Zealand</addr-line></nlm:aff><country xml:lang="fr">Nouvelle-Zélande</country><wicri:regionArea>Centre for Public Health Research, Massey University, Wellington</wicri:regionArea><wicri:noRegion>Wellington</wicri:noRegion></affiliation></author><author><name sortKey="Qu, Conghui" sort="Qu, Conghui" uniqKey="Qu C" first="Conghui" last="Qu">Conghui Qu</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Rosse, Stephanie A" sort="Rosse, Stephanie A" uniqKey="Rosse S" first="Stephanie A." last="Rosse">Stephanie A. Rosse</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name><affiliation wicri:level="2"><nlm:aff id="aff22"><addr-line>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Schumacher, Fred R" sort="Schumacher, Fred R" uniqKey="Schumacher F" first="Fred R." last="Schumacher">Fred R. Schumacher</name><affiliation wicri:level="4"><nlm:aff id="aff9"><addr-line>Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles, California</wicri:regionArea><placeName><region type="state">Californie</region><settlement type="city">Los Angeles</settlement></placeName><orgName type="university">Université de Californie du Sud</orgName></affiliation></author><author><name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name><affiliation wicri:level="2"><nlm:aff id="aff23"><addr-line>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name><affiliation wicri:level="2"><nlm:aff id="aff24"><addr-line>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff25"><addr-line>Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany</addr-line></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Zanke, Brent W" sort="Zanke, Brent W" uniqKey="Zanke B" first="Brent W." last="Zanke">Brent W. Zanke</name><affiliation wicri:level="1"><nlm:aff id="aff26"><addr-line>Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa</wicri:regionArea><wicri:noRegion>Ottawa</wicri:noRegion></affiliation></author><author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><affiliation wicri:level="2"><nlm:aff id="aff1"><addr-line>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff8"><addr-line>School of Public Health, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Public Health, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10<sup>−4</sup>). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×10<sup>−8</sup>. Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×10<sup>−6</sup>; Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tomlinson, I" uniqKey="Tomlinson I">I Tomlinson</name></author><author><name sortKey="Webb, E" uniqKey="Webb E">E Webb</name></author><author><name sortKey="Carvajal Carmona, L" uniqKey="Carvajal Carmona L">L Carvajal-Carmona</name></author><author><name sortKey="Broderick, P" uniqKey="Broderick P">P Broderick</name></author><author><name sortKey="Kemp, Z" uniqKey="Kemp Z">Z Kemp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zanke, Bw" uniqKey="Zanke B">BW Zanke</name></author><author><name sortKey="Greenwood, Cmt" uniqKey="Greenwood C">CMT Greenwood</name></author><author><name sortKey="Rangrej, J" uniqKey="Rangrej J">J Rangrej</name></author><author><name sortKey="Kustra, R" uniqKey="Kustra R">R 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(États-Unis)</li><li>Hawaï</li><li>Maryland</li><li>Massachusetts</li><li>Ohio</li><li>Ontario</li><li>Pays de la Loire</li><li>Pennsylvanie</li><li>Utah</li><li>Victoria (État)</li><li>Washington (État)</li><li>État de New York</li></region><settlement><li>Heidelberg</li><li>Los Angeles</li><li>Melbourne</li><li>Nantes</li><li>Seattle</li><li>Toronto</li></settlement><orgName><li>Université de Californie du Sud</li><li>Université de Melbourne</li><li>Université de Toronto</li><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Washington (État)"><name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name></region><name sortKey="Berndt, Sonja" sort="Berndt, Sonja" uniqKey="Berndt S" first="Sonja" last="Berndt">Sonja Berndt</name><name sortKey="Caan, Bette J" sort="Caan, Bette J" uniqKey="Caan B" first="Bette J." last="Caan">Bette J. 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Chan</name><name sortKey="Chanock, Stephen" sort="Chanock, Stephen" uniqKey="Chanock S" first="Stephen" last="Chanock">Stephen Chanock</name><name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name><name sortKey="Curtis, Keith R" sort="Curtis, Keith R" uniqKey="Curtis K" first="Keith R." last="Curtis">Keith R. Curtis</name><name sortKey="Duggan, David" sort="Duggan, David" uniqKey="Duggan D" first="David" last="Duggan">David Duggan</name><name sortKey="Gruber, Stephen B" sort="Gruber, Stephen B" uniqKey="Gruber S" first="Stephen B." last="Gruber">Stephen B. Gruber</name><name sortKey="Harrison, Tabitha A" sort="Harrison, Tabitha A" uniqKey="Harrison T" first="Tabitha A." last="Harrison">Tabitha A. Harrison</name><name sortKey="Hayes, Richard B" sort="Hayes, Richard B" uniqKey="Hayes R" first="Richard B." last="Hayes">Richard B. Hayes</name><name sortKey="Henderson, Brian E" sort="Henderson, Brian E" uniqKey="Henderson B" first="Brian E." last="Henderson">Brian E. Henderson</name><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name><name sortKey="Jackson, Rebecca D" sort="Jackson, Rebecca D" uniqKey="Jackson R" first="Rebecca D." last="Jackson">Rebecca D. Jackson</name><name sortKey="Kantor, Elizabeth D" sort="Kantor, Elizabeth D" uniqKey="Kantor E" first="Elizabeth D." last="Kantor">Elizabeth D. Kantor</name><name sortKey="Kolonel, Laurence N" sort="Kolonel, Laurence N" uniqKey="Kolonel L" first="Laurence N." last="Kolonel">Laurence N. Kolonel</name><name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name><name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name><name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name><name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name><name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name><name sortKey="Qu, Conghui" sort="Qu, Conghui" uniqKey="Qu C" first="Conghui" last="Qu">Conghui Qu</name><name sortKey="Rosse, Stephanie A" sort="Rosse, Stephanie A" uniqKey="Rosse S" first="Stephanie A." last="Rosse">Stephanie A. Rosse</name><name sortKey="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name><name sortKey="Schumacher, Fred R" sort="Schumacher, Fred R" uniqKey="Schumacher F" first="Fred R." last="Schumacher">Fred R. Schumacher</name><name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name><name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name></country><country name="France"><region name="Pays de la Loire"><name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name></region><name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name></region><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name><name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name></country><country name="Australie"><noRegion><name sortKey="Buchanan, Daniel" sort="Buchanan, Daniel" uniqKey="Buchanan D" first="Daniel" last="Buchanan">Daniel Buchanan</name></noRegion><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name></country><country name="Canada"><noRegion><name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name></noRegion><name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name><name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name><name sortKey="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name><name sortKey="Zanke, Brent W" sort="Zanke, Brent W" uniqKey="Zanke B" first="Brent W." last="Zanke">Brent W. Zanke</name></country><country name="Nouvelle-Zélande"><noRegion><name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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