Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21
Identifieur interne : 001E24 ( Pmc/Curation ); précédent : 001E23; suivant : 001E25Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21
Auteurs : Craig C. Teerlink [États-Unis] ; Daniel Leongamornlert [Royaume-Uni] ; Tokhir Dadaev [Royaume-Uni] ; Alun Thomas [États-Unis] ; James Farnham [États-Unis] ; Robert A. Stephenson [États-Unis] ; Shaun Riska [États-Unis] ; Shannon K. Mcdonnell [États-Unis] ; Daniel J. Schaid [États-Unis] ; William J. Catalona [États-Unis] ; S. Lilly Zheng [États-Unis] ; Kathleen A. Cooney [États-Unis] ; Anna M. Ray [États-Unis] ; Kimberly A. Zuhlke [États-Unis] ; Ethan M. Lange [États-Unis] ; Graham G. Giles [Australie] ; Melissa C. Southey [Australie] ; Liesel M. Fitzgerald [Australie] ; Antje Rinckleb [Allemagne] ; Manuel Luedeke [Allemagne] ; Christiane Maier [Allemagne] ; Janet L. Stanford [États-Unis] ; Elaine A. Ostrander [États-Unis] ; Elina M. Kaikkonen [Finlande] ; Csilla Sipeky [Finlande] ; Teuvo Tammela [Finlande] ; Johanna Schleutker [Finlande] ; Kathleen E. Wiley [États-Unis] ; Sarah D. Isaacs [États-Unis] ; Patrick C. Walsh [États-Unis] ; William B. Isaacs [États-Unis] ; Jianfeng Xu [États-Unis] ; Geraldine Cancel-Tassin [France] ; Olivier Cussenot [France] ; Diptasri Mandal [États-Unis] ; Cecelia Laurie [États-Unis] ; Cathy Laurie [États-Unis] ; Stephen N. Thibodeau [États-Unis] ; Rosalind A. Eeles [Royaume-Uni] ; Zsofia Kote-Jarai [Royaume-Uni] ; Lisa Cannon-Albright [États-Unis]Source :
- Human genetics [ 0340-6717 ] ; 2016.
Abstract
Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (
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DOI: 10.1007/s00439-016-1690-6
PubMed: 27262462
PubMed Central: 5020907
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Kaikkonen</name><affiliation wicri:level="1"><nlm:aff id="A20">Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Sipeky, Csilla" sort="Sipeky, Csilla" uniqKey="Sipeky C" first="Csilla" last="Sipeky">Csilla Sipeky</name><affiliation wicri:level="1"><nlm:aff id="A20">Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Tammela, Teuvo" sort="Tammela, Teuvo" uniqKey="Tammela T" first="Teuvo" last="Tammela">Teuvo Tammela</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Urology, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Urology, University of Tampere and Tampere University Hospital, 33520 Tampere</wicri:regionArea></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation wicri:level="1"><nlm:aff id="A22">Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Wiley, Kathleen E" sort="Wiley, Kathleen E" uniqKey="Wiley K" first="Kathleen E." last="Wiley">Kathleen E. Wiley</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Isaacs, Sarah D" sort="Isaacs, Sarah D" uniqKey="Isaacs S" first="Sarah D." last="Isaacs">Sarah D. Isaacs</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, Patrick C" sort="Walsh, Patrick C" uniqKey="Walsh P" first="Patrick C." last="Walsh">Patrick C. Walsh</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Isaacs, William B" sort="Isaacs, William B" uniqKey="Isaacs W" first="William B." last="Isaacs">William B. 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Thibodeau</name><affiliation wicri:level="1"><nlm:aff id="A28">Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN 55905</wicri:regionArea></affiliation></author><author><name sortKey="Eeles, Rosalind A" sort="Eeles, Rosalind A" uniqKey="Eeles R" first="Rosalind A." last="Eeles">Rosalind A. Eeles</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Cannon Albright, Lisa" sort="Cannon Albright, Lisa" uniqKey="Cannon Albright L" first="Lisa" last="Cannon-Albright">Lisa Cannon-Albright</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A29">George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27262462</idno><idno type="pmc">5020907</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020907</idno><idno type="RBID">PMC:5020907</idno><idno type="doi">10.1007/s00439-016-1690-6</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">001F70</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001F70</idno><idno type="wicri:Area/Pmc/Curation">001E24</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001E24</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21</title><author><name sortKey="Teerlink, Craig C" sort="Teerlink, Craig C" uniqKey="Teerlink C" first="Craig C." last="Teerlink">Craig C. Teerlink</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108</wicri:regionArea></affiliation></author><author><name sortKey="Leongamornlert, Daniel" sort="Leongamornlert, Daniel" uniqKey="Leongamornlert D" first="Daniel" last="Leongamornlert">Daniel Leongamornlert</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Dadaev, Tokhir" sort="Dadaev, Tokhir" uniqKey="Dadaev T" first="Tokhir" last="Dadaev">Tokhir Dadaev</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Thomas, Alun" sort="Thomas, Alun" uniqKey="Thomas A" first="Alun" last="Thomas">Alun Thomas</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108</wicri:regionArea></affiliation></author><author><name sortKey="Farnham, James" sort="Farnham, James" uniqKey="Farnham J" first="James" last="Farnham">James Farnham</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108</wicri:regionArea></affiliation></author><author><name sortKey="Stephenson, Robert A" sort="Stephenson, Robert A" uniqKey="Stephenson R" first="Robert A." last="Stephenson">Robert A. Stephenson</name><affiliation wicri:level="1"><nlm:aff id="A3">Department of Urology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, University of Utah School of Medicine, Salt Lake City, UT 84132</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A4">Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84132, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84132</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112</wicri:regionArea></affiliation></author><author><name sortKey="Riska, Shaun" sort="Riska, Shaun" uniqKey="Riska S" first="Shaun" last="Riska">Shaun Riska</name><affiliation wicri:level="1"><nlm:aff id="A6">Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905</wicri:regionArea></affiliation></author><author><name sortKey="Mcdonnell, Shannon K" sort="Mcdonnell, Shannon K" uniqKey="Mcdonnell S" first="Shannon K." last="Mcdonnell">Shannon K. Mcdonnell</name><affiliation wicri:level="1"><nlm:aff id="A6">Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905</wicri:regionArea></affiliation></author><author><name sortKey="Schaid, Daniel J" sort="Schaid, Daniel J" uniqKey="Schaid D" first="Daniel J." last="Schaid">Daniel J. Schaid</name><affiliation wicri:level="1"><nlm:aff id="A6">Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905</wicri:regionArea></affiliation></author><author><name sortKey="Catalona, William J" sort="Catalona, William J" uniqKey="Catalona W" first="William J." last="Catalona">William J. Catalona</name><affiliation wicri:level="1"><nlm:aff id="A7">Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Feinberg School of Medicine, Northwestern University, Chicago, IL 60611</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, S Lilly" sort="Zheng, S Lilly" uniqKey="Zheng S" first="S. Lilly" last="Zheng">S. Lilly Zheng</name><affiliation wicri:level="1"><nlm:aff id="A7">Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Feinberg School of Medicine, Northwestern University, Chicago, IL 60611</wicri:regionArea></affiliation></author><author><name sortKey="Cooney, Kathleen A" sort="Cooney, Kathleen A" uniqKey="Cooney K" first="Kathleen A." last="Cooney">Kathleen A. Cooney</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation></author><author><name sortKey="Ray, Anna M" sort="Ray, Anna M" uniqKey="Ray A" first="Anna M." last="Ray">Anna M. Ray</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation></author><author><name sortKey="Zuhlke, Kimberly A" sort="Zuhlke, Kimberly A" uniqKey="Zuhlke K" first="Kimberly A." last="Zuhlke">Kimberly A. Zuhlke</name><affiliation wicri:level="1"><nlm:aff id="A8">Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109</wicri:regionArea></affiliation></author><author><name sortKey="Lange, Ethan M" sort="Lange, Ethan M" uniqKey="Lange E" first="Ethan M." last="Lange">Ethan M. Lange</name><affiliation wicri:level="1"><nlm:aff id="A10">Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A11">Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation wicri:level="1"><nlm:aff id="A12">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne 3004, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne 3004</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC 3010, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC 3010</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004</wicri:regionArea></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation wicri:level="1"><nlm:aff id="A15">Department of Pathology, University of Melbourne, Melbourne 3010, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Pathology, University of Melbourne, Melbourne 3010</wicri:regionArea></affiliation></author><author><name sortKey="Fitzgerald, Liesel M" sort="Fitzgerald, Liesel M" uniqKey="Fitzgerald L" first="Liesel M." last="Fitzgerald">Liesel M. Fitzgerald</name><affiliation wicri:level="1"><nlm:aff id="A12">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne 3004, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne 3004</wicri:regionArea></affiliation></author><author><name sortKey="Rinckleb, Antje" sort="Rinckleb, Antje" uniqKey="Rinckleb A" first="Antje" last="Rinckleb">Antje Rinckleb</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Urology, University Hospital Ulm, 53179 Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm, 53179 Ulm</wicri:regionArea></affiliation></author><author><name sortKey="Luedeke, Manuel" sort="Luedeke, Manuel" uniqKey="Luedeke M" first="Manuel" last="Luedeke">Manuel Luedeke</name><affiliation wicri:level="1"><nlm:aff id="A16">Department of Urology, University Hospital Ulm, 53179 Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, University Hospital Ulm, 53179 Ulm</wicri:regionArea></affiliation></author><author><name sortKey="Maier, Christiane" sort="Maier, Christiane" uniqKey="Maier C" first="Christiane" last="Maier">Christiane Maier</name><affiliation wicri:level="1"><nlm:aff id="A17">Institute for Human Genetics, University of Ulm, 89081 Ulm, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Human Genetics, University of Ulm, 89081 Ulm</wicri:regionArea></affiliation></author><author><name sortKey="Stanford, Janet L" sort="Stanford, Janet L" uniqKey="Stanford J" first="Janet L." last="Stanford">Janet L. Stanford</name><affiliation wicri:level="1"><nlm:aff id="A18">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109</wicri:regionArea></affiliation></author><author><name sortKey="Ostrander, Elaine A" sort="Ostrander, Elaine A" uniqKey="Ostrander E" first="Elaine A." last="Ostrander">Elaine A. Ostrander</name><affiliation wicri:level="1"><nlm:aff id="A19">Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD 20892, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD 20892</wicri:regionArea></affiliation></author><author><name sortKey="Kaikkonen, Elina M" sort="Kaikkonen, Elina M" uniqKey="Kaikkonen E" first="Elina M." last="Kaikkonen">Elina M. Kaikkonen</name><affiliation wicri:level="1"><nlm:aff id="A20">Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Sipeky, Csilla" sort="Sipeky, Csilla" uniqKey="Sipeky C" first="Csilla" last="Sipeky">Csilla Sipeky</name><affiliation wicri:level="1"><nlm:aff id="A20">Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Tammela, Teuvo" sort="Tammela, Teuvo" uniqKey="Tammela T" first="Teuvo" last="Tammela">Teuvo Tammela</name><affiliation wicri:level="1"><nlm:aff id="A21">Department of Urology, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Department of Urology, University of Tampere and Tampere University Hospital, 33520 Tampere</wicri:regionArea></affiliation></author><author><name sortKey="Schleutker, Johanna" sort="Schleutker, Johanna" uniqKey="Schleutker J" first="Johanna" last="Schleutker">Johanna Schleutker</name><affiliation wicri:level="1"><nlm:aff id="A22">Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20520 Turku, Finland</nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20520 Turku</wicri:regionArea></affiliation></author><author><name sortKey="Wiley, Kathleen E" sort="Wiley, Kathleen E" uniqKey="Wiley K" first="Kathleen E." last="Wiley">Kathleen E. Wiley</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Isaacs, Sarah D" sort="Isaacs, Sarah D" uniqKey="Isaacs S" first="Sarah D." last="Isaacs">Sarah D. Isaacs</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, Patrick C" sort="Walsh, Patrick C" uniqKey="Walsh P" first="Patrick C." last="Walsh">Patrick C. Walsh</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Isaacs, William B" sort="Isaacs, William B" uniqKey="Isaacs W" first="William B." last="Isaacs">William B. Isaacs</name><affiliation wicri:level="1"><nlm:aff id="A23">Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Jianfeng" sort="Xu, Jianfeng" uniqKey="Xu J" first="Jianfeng" last="Xu">Jianfeng Xu</name><affiliation wicri:level="1"><nlm:aff id="A24">Program for Personalized Cancer Care, NorthShore University Health System, Evanston, IL 60201, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Program for Personalized Cancer Care, NorthShore University Health System, Evanston, IL 60201</wicri:regionArea></affiliation></author><author><name sortKey="Cancel Tassin, Geraldine" sort="Cancel Tassin, Geraldine" uniqKey="Cancel Tassin G" first="Geraldine" last="Cancel-Tassin">Geraldine Cancel-Tassin</name><affiliation wicri:level="1"><nlm:aff id="A25">CeRePP, Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CeRePP, Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Cussenot, Olivier" sort="Cussenot, Olivier" uniqKey="Cussenot O" first="Olivier" last="Cussenot">Olivier Cussenot</name><affiliation wicri:level="1"><nlm:aff id="A25">CeRePP, Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>CeRePP, Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Mandal, Diptasri" sort="Mandal, Diptasri" uniqKey="Mandal D" first="Diptasri" last="Mandal">Diptasri Mandal</name><affiliation wicri:level="1"><nlm:aff id="A26">Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112</wicri:regionArea></affiliation></author><author><name sortKey="Laurie, Cecelia" sort="Laurie, Cecelia" uniqKey="Laurie C" first="Cecelia" last="Laurie">Cecelia Laurie</name><affiliation wicri:level="1"><nlm:aff id="A27">Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, University of Washington, Seattle, WA 98195</wicri:regionArea></affiliation></author><author><name sortKey="Laurie, Cathy" sort="Laurie, Cathy" uniqKey="Laurie C" first="Cathy" last="Laurie">Cathy Laurie</name><affiliation wicri:level="1"><nlm:aff id="A27">Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics, University of Washington, Seattle, WA 98195</wicri:regionArea></affiliation></author><author><name sortKey="Thibodeau, Stephen N" sort="Thibodeau, Stephen N" uniqKey="Thibodeau S" first="Stephen N." last="Thibodeau">Stephen N. Thibodeau</name><affiliation wicri:level="1"><nlm:aff id="A28">Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN 55905</wicri:regionArea></affiliation></author><author><name sortKey="Eeles, Rosalind A" sort="Eeles, Rosalind A" uniqKey="Eeles R" first="Rosalind A." last="Eeles">Rosalind A. Eeles</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Kote Jarai, Zsofia" sort="Kote Jarai, Zsofia" uniqKey="Kote Jarai Z" first="Zsofia" last="Kote-Jarai">Zsofia Kote-Jarai</name><affiliation wicri:level="1"><nlm:aff id="A2">Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP</wicri:regionArea></affiliation></author><author><name sortKey="Cannon Albright, Lisa" sort="Cannon Albright, Lisa" uniqKey="Cannon Albright L" first="Lisa" last="Cannon-Albright">Lisa Cannon-Albright</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A29">George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148</wicri:regionArea></affiliation></author></analytic><series><title level="j">Human genetics</title><idno type="ISSN">0340-6717</idno><idno type="eISSN">1432-1203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (<italic>p</italic> = 1.7e<sup>−8</sup>) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (<italic>p</italic> = 8.5e<sup>−11</sup>). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7613873</journal-id><journal-id journal-id-type="pubmed-jr-id">4137</journal-id><journal-id journal-id-type="nlm-ta">Hum Genet</journal-id><journal-id journal-id-type="iso-abbrev">Hum. Genet.</journal-id><journal-title-group><journal-title>Human genetics</journal-title></journal-title-group><issn pub-type="ppub">0340-6717</issn><issn pub-type="epub">1432-1203</issn></journal-meta><article-meta><article-id pub-id-type="pmid">27262462</article-id><article-id pub-id-type="pmc">5020907</article-id><article-id pub-id-type="doi">10.1007/s00439-016-1690-6</article-id><article-id pub-id-type="manuscript">NIHMS814106</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Teerlink</surname><given-names>Craig C.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Leongamornlert</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dadaev</surname><given-names>Tokhir</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>Alun</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Farnham</surname><given-names>James</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stephenson</surname><given-names>Robert A.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Riska</surname><given-names>Shaun</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>McDonnell</surname><given-names>Shannon K.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Schaid</surname><given-names>Daniel J.</given-names></name><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Catalona</surname><given-names>William J.</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>S. Lilly</given-names></name><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Cooney</surname><given-names>Kathleen A.</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Ray</surname><given-names>Anna M.</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Zuhlke</surname><given-names>Kimberly A.</given-names></name><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Lange</surname><given-names>Ethan M.</given-names></name><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Giles</surname><given-names>Graham G.</given-names></name><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Southey</surname><given-names>Melissa C.</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Fitzgerald</surname><given-names>Liesel M.</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Rinckleb</surname><given-names>Antje</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Luedeke</surname><given-names>Manuel</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Maier</surname><given-names>Christiane</given-names></name><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Stanford</surname><given-names>Janet L.</given-names></name><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Ostrander</surname><given-names>Elaine A.</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Kaikkonen</surname><given-names>Elina M.</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Sipeky</surname><given-names>Csilla</given-names></name><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Tammela</surname><given-names>Teuvo</given-names></name><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Schleutker</surname><given-names>Johanna</given-names></name><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Wiley</surname><given-names>Kathleen E.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Isaacs</surname><given-names>Sarah D.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Walsh</surname><given-names>Patrick C.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Isaacs</surname><given-names>William B.</given-names></name><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Jianfeng</given-names></name><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Cancel-Tassin</surname><given-names>Geraldine</given-names></name><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Cussenot</surname><given-names>Olivier</given-names></name><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Mandal</surname><given-names>Diptasri</given-names></name><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Laurie</surname><given-names>Cecelia</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Laurie</surname><given-names>Cathy</given-names></name><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><collab>The PRACTICAL consortium</collab></contrib><contrib contrib-type="author"><collab>International Consortium for Prostate Cancer Genetics</collab></contrib><contrib contrib-type="author"><name><surname>Thibodeau</surname><given-names>Stephen N.</given-names></name><xref ref-type="aff" rid="A28">28</xref></contrib><contrib contrib-type="author"><name><surname>Eeles</surname><given-names>Rosalind A.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kote-Jarai</surname><given-names>Zsofia</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cannon-Albright</surname><given-names>Lisa</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A29">29</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA</aff><aff id="A2"><label>2</label>Division of Genetics and Epidemiology, Institute of Cancer Research, London SW7 3RP, UK</aff><aff id="A3"><label>3</label>Department of Urology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA</aff><aff id="A4"><label>4</label>Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT 84132, USA</aff><aff id="A5"><label>5</label>Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA</aff><aff id="A6"><label>6</label>Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA</aff><aff id="A7"><label>7</label>Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA</aff><aff id="A8"><label>8</label>Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA</aff><aff id="A9"><label>9</label>Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA</aff><aff id="A10"><label>10</label>Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA</aff><aff id="A11"><label>11</label>Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA</aff><aff id="A12"><label>12</label>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne 3004, Australia</aff><aff id="A13"><label>13</label>Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC 3010, Australia</aff><aff id="A14"><label>14</label>Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia</aff><aff id="A15"><label>15</label>Department of Pathology, University of Melbourne, Melbourne 3010, Australia</aff><aff id="A16"><label>16</label>Department of Urology, University Hospital Ulm, 53179 Ulm, Germany</aff><aff id="A17"><label>17</label>Institute for Human Genetics, University of Ulm, 89081 Ulm, Germany</aff><aff id="A18"><label>18</label>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109, USA</aff><aff id="A19"><label>19</label>Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD 20892, USA</aff><aff id="A20"><label>20</label>Department of Medical Biochemistry and Genetics, University of Turku, 20520 Turku, Finland</aff><aff id="A21"><label>21</label>Department of Urology, University of Tampere and Tampere University Hospital, 33520 Tampere, Finland</aff><aff id="A22"><label>22</label>Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, 20520 Turku, Finland</aff><aff id="A23"><label>23</label>Brady Urological Institute, Johns Hopkins University, Baltimore, MD 21287, USA</aff><aff id="A24"><label>24</label>Program for Personalized Cancer Care, NorthShore University Health System, Evanston, IL 60201, USA</aff><aff id="A25"><label>25</label>CeRePP, Hopital Tenon, Assistance Publique-Hopitaux de Paris, 75020 Paris, France</aff><aff id="A26"><label>26</label>Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA</aff><aff id="A27"><label>27</label>Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</aff><aff id="A28"><label>28</label>Department of Lab Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA</aff><aff id="A29"><label>29</label>George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA</aff><author-notes><corresp id="CR1">Craig C. Teerlink, <email>craig.teerlink@utah.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>5</day><month>9</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>04</day><month>6</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>8</month><year>2017</year></pub-date><volume>135</volume><issue>8</issue><fpage>923</fpage><lpage>938</lpage><pmc-comment>elocation-id from pubmed: 10.1007/s00439-016-1690-6</pmc-comment>
<abstract><p id="P1">Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (<italic>p</italic> = 1.7e<sup>−8</sup>) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (<italic>p</italic> = 8.5e<sup>−11</sup>). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer pre-disposition locus.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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