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Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk

Identifieur interne : 006441 ( Main/Merge ); précédent : 006440; suivant : 006442

Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk

Auteurs : Ulrike Peters [États-Unis] ; Carolyn M. Hutter [États-Unis] ; Li Hsu [États-Unis] ; Fredrick R. Schumacher [États-Unis] ; David V. Conti [États-Unis] ; Christopher S. Carlson [États-Unis] ; Christopher K. Edlund [États-Unis] ; Robert W. Haile [États-Unis] ; Steven Gallinger [Canada] ; Brent W. Zanke [Canada] ; Mathieu Lemire [Canada] ; Jagadish Rangrej [Canada] ; Raakhee Vijayaraghavan [États-Unis] ; Andrew T. Chan [États-Unis] ; Aditi Hazra [États-Unis] ; David J. Hunter [États-Unis] ; Jing Ma [États-Unis] ; Charles S. Fuchs [États-Unis] ; Edward L. Giovannucci [États-Unis] ; Peter Kraft [États-Unis] ; Yan Liu [États-Unis] ; Lin Chen [États-Unis] ; Shuo Jiao [États-Unis] ; Karen W. Makar [États-Unis] ; Darin Taverna [États-Unis] ; Stephen B. Gruber [États-Unis] ; Gad Rennert [Israël] ; Victor Moreno [Espagne] ; Cornelia M. Ulrich [États-Unis, Allemagne] ; Michael O. Woods [Canada] ; Roger C. Green [Canada] ; Patrick S. Parfrey [Canada] ; Ross L. Prentice [États-Unis] ; Charles Kooperberg [États-Unis] ; Rebecca D. Jackson [États-Unis] ; Andrea Z. Lacroix [États-Unis] ; Bette J. Caan [États-Unis] ; Richard B. Hayes [États-Unis] ; Sonja I. Berndt [États-Unis] ; Stephen J. Chanock [États-Unis] ; Robert E. Schoen [États-Unis] ; Jenny Chang-Claude [Allemagne] ; Michael Hoffmeister [Allemagne] ; Hermann Brenner [Allemagne] ; Bernd Frank [Allemagne] ; Stéphane Bézieau [France] ; Sébastien Küry [France] ; Martha L. Slattery [États-Unis] ; John L. Hopper [Australie] ; Mark A. Jenkins [Australie] ; Loic Le Marchand [États-Unis] ; Noralane M. Lindor [États-Unis] ; Polly A. Newcomb [États-Unis] ; Daniela Seminara [États-Unis] ; Thomas J. Hudson [Canada] ; David J. Duggan [États-Unis] ; John D. Potter [États-Unis] ; Graham Casey [États-Unis]

Source :

RBID : PMC:3257356

Abstract

Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow-up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for genome-wide association studies (GWAS) of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using 10 independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured 10 SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p-value range: 0.02 to 1.8 × 10−8). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p<0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p-value 0.03; combined p-value 7.3 × 10−5). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p-value 0.03; combined p-value 1.9 × 10−4). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.


Url:
DOI: 10.1007/s00439-011-1055-0
PubMed: 21761138
PubMed Central: 3257356

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PMC:3257356

Le document en format XML

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<name sortKey="Giovannucci, Edward L" sort="Giovannucci, Edward L" uniqKey="Giovannucci E" first="Edward L." last="Giovannucci">Edward L. Giovannucci</name>
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<wicri:regionArea>Quantitative Services, Baylor Health Care System, Dallas</wicri:regionArea>
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<settlement type="city">Dallas</settlement>
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<name sortKey="Chen, Lin" sort="Chen, Lin" uniqKey="Chen L" first="Lin" last="Chen">Lin Chen</name>
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<nlm:aff id="A16">Department of Health Studies, University of Chicago, Chicago, USA</nlm:aff>
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<wicri:regionArea>Department of Health Studies, University of Chicago, Chicago</wicri:regionArea>
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<settlement type="city">Chicago</settlement>
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<name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name>
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<name sortKey="Makar, Karen W" sort="Makar, Karen W" uniqKey="Makar K" first="Karen W." last="Makar">Karen W. Makar</name>
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<name sortKey="Taverna, Darin" sort="Taverna, Darin" uniqKey="Taverna D" first="Darin" last="Taverna">Darin Taverna</name>
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<name sortKey="Gruber, Stephen B" sort="Gruber, Stephen B" uniqKey="Gruber S" first="Stephen B." last="Gruber">Stephen B. Gruber</name>
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<nlm:aff id="A17">Department of Internal Medicine, University of Michigan, Ann Arbor, USA</nlm:aff>
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<wicri:regionArea>Department of Internal Medicine, University of Michigan, Ann Arbor</wicri:regionArea>
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<name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name>
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<country xml:lang="fr">Israël</country>
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<name sortKey="Moreno, Victor" sort="Moreno, Victor" uniqKey="Moreno V" first="Victor" last="Moreno">Victor Moreno</name>
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<nlm:aff id="A19">Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona</wicri:regionArea>
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<settlement type="city">Barcelone</settlement>
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<name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name>
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<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
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<wicri:regionArea>Department of Epidemiology, School of Public Health, University of Washington, Seattle</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
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<settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
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<nlm:aff id="A20">Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Preventive Oncology, 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>
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<name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name>
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<name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
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<name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name>
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<nlm:aff id="A32">Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, USA</nlm:aff>
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<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
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<nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
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<nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
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<name sortKey="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
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<nlm:aff id="A34">Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu, USA</nlm:aff>
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<name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M." last="Lindor">Noralane M. Lindor</name>
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<nlm:aff id="A35">Department of Medical Genetics, Mayo Clinic, Rochester, USA</nlm:aff>
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<wicri:regionArea>Department of Medical Genetics, Mayo Clinic, Rochester</wicri:regionArea>
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<name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name>
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<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
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<name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
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<nlm:aff id="A36">Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, USA</nlm:aff>
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<name sortKey="Hudson, Thomas J" sort="Hudson, Thomas J" uniqKey="Hudson T" first="Thomas J." last="Hudson">Thomas J. Hudson</name>
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<nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</nlm:aff>
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<name sortKey="Duggan, David J" sort="Duggan, David J" uniqKey="Duggan D" first="David J." last="Duggan">David J. Duggan</name>
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<nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
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<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
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<nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
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<nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
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<name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
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<name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name>
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<name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name>
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<name sortKey="Edlund, Christopher K" sort="Edlund, Christopher K" uniqKey="Edlund C" first="Christopher K." last="Edlund">Christopher K. Edlund</name>
<affiliation wicri:level="4">
<nlm:aff id="A5">Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Keck School of Medicine, University of Southern California, Los Angeles</wicri:regionArea>
<placeName>
<settlement type="city">Los Angeles</settlement>
<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="Haile, Robert W" sort="Haile, Robert W" uniqKey="Haile R" first="Robert W." last="Haile">Robert W. Haile</name>
<affiliation wicri:level="4">
<nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles</wicri:regionArea>
<placeName>
<settlement type="city">Los Angeles</settlement>
<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="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name>
<affiliation wicri:level="1">
<nlm:aff id="A6">Department of Surgery, University Health Network, Toronto General Hospital, Toronto, Canada</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="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="A7">Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada</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="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name>
<affiliation wicri:level="1">
<nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</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="Rangrej, Jagadish" sort="Rangrej, Jagadish" uniqKey="Rangrej J" first="Jagadish" last="Rangrej">Jagadish Rangrej</name>
<affiliation wicri:level="1">
<nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</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="Vijayaraghavan, Raakhee" sort="Vijayaraghavan, Raakhee" uniqKey="Vijayaraghavan R" first="Raakhee" last="Vijayaraghavan">Raakhee Vijayaraghavan</name>
<affiliation wicri:level="1">
<nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Translational Genomics Research Institute, Phoenix</wicri:regionArea>
<wicri:noRegion>Phoenix</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chan, Andrew T" sort="Chan, Andrew T" uniqKey="Chan A" first="Andrew T." last="Chan">Andrew T. Chan</name>
<affiliation wicri:level="3">
<nlm:aff id="A10">Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hazra, Aditi" sort="Hazra, Aditi" uniqKey="Hazra A" first="Aditi" last="Hazra">Aditi Hazra</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name>
<affiliation wicri:level="3">
<nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Ma, Jing" sort="Ma, Jing" uniqKey="Ma J" first="Jing" last="Ma">Jing Ma</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Fuchs, Charles S" sort="Fuchs, Charles S" uniqKey="Fuchs C" first="Charles S." last="Fuchs">Charles S. Fuchs</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A13">Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Giovannucci, Edward L" sort="Giovannucci, Edward L" uniqKey="Giovannucci E" first="Edward L." last="Giovannucci">Edward L. Giovannucci</name>
<affiliation wicri:level="3">
<nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A14">Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name>
<affiliation wicri:level="3">
<nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston</wicri:regionArea>
<placeName>
<settlement type="city">Boston</settlement>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name>
<affiliation wicri:level="3">
<nlm:aff id="A15">Quantitative Services, Baylor Health Care System, Dallas, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Quantitative Services, Baylor Health Care System, Dallas</wicri:regionArea>
<placeName>
<settlement type="city">Dallas</settlement>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Chen, Lin" sort="Chen, Lin" uniqKey="Chen L" first="Lin" last="Chen">Lin Chen</name>
<affiliation wicri:level="3">
<nlm:aff id="A16">Department of Health Studies, University of Chicago, Chicago, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Health Studies, University of Chicago, Chicago</wicri:regionArea>
<placeName>
<settlement type="city">Chicago</settlement>
<region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Makar, Karen W" sort="Makar, Karen W" uniqKey="Makar K" first="Karen W." last="Makar">Karen W. Makar</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Taverna, Darin" sort="Taverna, Darin" uniqKey="Taverna D" first="Darin" last="Taverna">Darin Taverna</name>
<affiliation wicri:level="1">
<nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Translational Genomics Research Institute, Phoenix</wicri:regionArea>
<wicri:noRegion>Phoenix</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="1">
<nlm:aff id="A17">Department of Internal Medicine, University of Michigan, Ann Arbor, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Internal Medicine, University of Michigan, Ann Arbor</wicri:regionArea>
<wicri:noRegion>Ann Arbor</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Department of Community Medicine and Epidemiology, CarmelMedical Center and Technion Faculty of Medicine, Haifa, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Department of Community Medicine and Epidemiology, CarmelMedical Center and Technion Faculty of Medicine, Haifa</wicri:regionArea>
<wicri:noRegion>Haifa</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Moreno, Victor" sort="Moreno, Victor" uniqKey="Moreno V" first="Victor" last="Moreno">Victor Moreno</name>
<affiliation wicri:level="3">
<nlm:aff id="A19">Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona</wicri:regionArea>
<placeName>
<settlement type="city">Barcelone</settlement>
<region nuts="2" type="region">Catalogne</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="1">
<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, School of Public Health, University of Washington, Seattle</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
<placeName>
<settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A20">Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Preventive Oncology, 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="Woods, Michael O" sort="Woods, Michael O" uniqKey="Woods M" first="Michael O." last="Woods">Michael O. Woods</name>
<affiliation wicri:level="1">
<nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s</wicri:regionArea>
<wicri:noRegion>St. John’s</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Green, Roger C" sort="Green, Roger C" uniqKey="Green R" first="Roger C." last="Green">Roger C. Green</name>
<affiliation wicri:level="1">
<nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s</wicri:regionArea>
<wicri:noRegion>St. John’s</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Parfrey, Patrick S" sort="Parfrey, Patrick S" uniqKey="Parfrey P" first="Patrick S." last="Parfrey">Patrick S. Parfrey</name>
<affiliation wicri:level="1">
<nlm:aff id="A22">Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s</wicri:regionArea>
<wicri:noRegion>St. John’s</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Prentice, Ross L" sort="Prentice, Ross L" uniqKey="Prentice R" first="Ross L." last="Prentice">Ross L. Prentice</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Kooperberg, Charles" sort="Kooperberg, Charles" uniqKey="Kooperberg C" first="Charles" last="Kooperberg">Charles Kooperberg</name>
<affiliation wicri:level="1">
<nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</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="1">
<nlm:aff id="A24">Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus</wicri:regionArea>
<wicri:noRegion>Columbus</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lacroix, Andrea Z" sort="Lacroix, Andrea Z" uniqKey="Lacroix A" first="Andrea Z." last="Lacroix">Andrea Z. Lacroix</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</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="1">
<nlm:aff id="A25">Division of Research, Kaiser Permanente Medical Care Program, Oakland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Research, Kaiser Permanente Medical Care Program, Oakland</wicri:regionArea>
<wicri:noRegion>Oakland</wicri:noRegion>
</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="3">
<nlm:aff id="A26">Division of Epidemiology, Department of Environmental Medicine, New YorkUniversity School of Medicine, New York City, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Epidemiology, Department of Environmental Medicine, New YorkUniversity School of Medicine, New York City</wicri:regionArea>
<placeName>
<settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Berndt, Sonja I" sort="Berndt, Sonja I" uniqKey="Berndt S" first="Sonja I." last="Berndt">Sonja I. Berndt</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda</wicri:regionArea>
<wicri:noRegion>Bethesda</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J." last="Chanock">Stephen J. Chanock</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda</wicri:regionArea>
<wicri:noRegion>Bethesda</wicri:noRegion>
</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="3">
<nlm:aff id="A28">Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh</wicri:regionArea>
<placeName>
<settlement type="city">Pittsburgh</settlement>
<region type="state">Pennsylvanie</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="A29">Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany</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="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name>
<affiliation wicri:level="3">
<nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</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="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name>
<affiliation wicri:level="3">
<nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</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="Frank, Bernd" sort="Frank, Bernd" uniqKey="Frank B" first="Bernd" last="Frank">Bernd Frank</name>
<affiliation wicri:level="3">
<nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</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="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name>
<affiliation wicri:level="3">
<nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, 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="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
<affiliation wicri:level="3">
<nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, 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="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name>
<affiliation wicri:level="1">
<nlm:aff id="A32">Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City</wicri:regionArea>
<wicri:noRegion>Salt Lake City</wicri:noRegion>
</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="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, 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="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="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, 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="Le Marchand, Loic" sort="Le Marchand, Loic" uniqKey="Le Marchand L" first="Loic" last="Le Marchand">Loic Le Marchand</name>
<affiliation wicri:level="1">
<nlm:aff id="A34">Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu</wicri:regionArea>
<wicri:noRegion>Honolulu</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M." last="Lindor">Noralane M. Lindor</name>
<affiliation wicri:level="1">
<nlm:aff id="A35">Department of Medical Genetics, Mayo Clinic, Rochester, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medical Genetics, Mayo Clinic, Rochester</wicri:regionArea>
<wicri:noRegion>Rochester</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="1">
<nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<affiliation wicri:level="1">
<nlm:aff id="A36">Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda</wicri:regionArea>
<wicri:noRegion>Bethesda</wicri:noRegion>
</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="A8">Ontario Institute for Cancer Research, Toronto, Canada</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="A37">Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</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="Duggan, David J" sort="Duggan, David J" uniqKey="Duggan D" first="David J." last="Duggan">David J. Duggan</name>
<affiliation wicri:level="1">
<nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Translational Genomics Research Institute, Phoenix</wicri:regionArea>
<wicri:noRegion>Phoenix</wicri:noRegion>
</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="4">
<nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology, School of Public Health, University of Washington, Seattle</wicri:regionArea>
<orgName type="university">Université de Washington</orgName>
<placeName>
<settlement type="city">Seattle</settlement>
<region type="state">Washington (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle</wicri:regionArea>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Casey, Graham" sort="Casey, Graham" uniqKey="Casey G" first="Graham" last="Casey">Graham Casey</name>
<affiliation wicri:level="4">
<nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles</wicri:regionArea>
<placeName>
<settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</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="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P1">Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow-up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for genome-wide association studies (GWAS) of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using 10 independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured 10 SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p-value range: 0.02 to 1.8 × 10
<sup>−8</sup>
). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p<0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the
<italic>BMP2</italic>
region at chromosomal location 20p12 (rs4813802; replication p-value 0.03; combined p-value 7.3 × 10
<sup>−5</sup>
). In a region on 5p33.15, which includes the coding regions of the
<italic>TERT-CLPTM1L</italic>
genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p-value 0.03; combined p-value 1.9 × 10
<sup>−4</sup>
). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.</p>
</div>
</front>
</TEI>
</record>

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