Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk
Identifieur interne : 001546 ( Pmc/Corpus ); précédent : 001545; suivant : 001547Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk
Auteurs : Ulrike Peters ; Carolyn M. Hutter ; Li Hsu ; Fredrick R. Schumacher ; David V. Conti ; Christopher S. Carlson ; Christopher K. Edlund ; Robert W. Haile ; Steven Gallinger ; Brent W. Zanke ; Mathieu Lemire ; Jagadish Rangrej ; Raakhee Vijayaraghavan ; Andrew T. Chan ; Aditi Hazra ; David J. Hunter ; Jing Ma ; Charles S. Fuchs ; Edward L. Giovannucci ; Peter Kraft ; Yan Liu ; Lin Chen ; Shuo Jiao ; Karen W. Makar ; Darin Taverna ; Stephen B. Gruber ; Gad Rennert ; Victor Moreno ; Cornelia M. Ulrich ; Michael O. Woods ; Roger C. Green ; Patrick S. Parfrey ; Ross L. Prentice ; Charles Kooperberg ; Rebecca D. Jackson ; Andrea Z. Lacroix ; Bette J. Caan ; Richard B. Hayes ; Sonja I. Berndt ; Stephen J. Chanock ; Robert E. Schoen ; Jenny Chang-Claude ; Michael Hoffmeister ; Hermann Brenner ; Bernd Frank ; Stéphane Bézieau ; Sébastien Küry ; Martha L. Slattery ; John L. Hopper ; Mark A. Jenkins ; Loic Le Marchand ; Noralane M. Lindor ; Polly A. Newcomb ; Daniela Seminara ; Thomas J. Hudson ; David J. Duggan ; John D. Potter ; Graham CaseySource :
- Human Genetics [ 0340-6717 ] ; 2011.
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
Url:
DOI: 10.1007/s00439-011-1055-0
PubMed: 21761138
PubMed Central: 3257356
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PMC:3257356Le document en format XML
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<author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
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<affiliation><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
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<author><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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<author><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name>
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<author><name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<affiliation><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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<author><name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name>
<affiliation><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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<author><name sortKey="Carlson, Christopher S" sort="Carlson, Christopher S" uniqKey="Carlson C" first="Christopher S." last="Carlson">Christopher S. Carlson</name>
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<author><name sortKey="Edlund, Christopher K" sort="Edlund, Christopher K" uniqKey="Edlund C" first="Christopher K." last="Edlund">Christopher K. Edlund</name>
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<author><name sortKey="Haile, Robert W" sort="Haile, Robert W" uniqKey="Haile R" first="Robert W." last="Haile">Robert W. Haile</name>
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<author><name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name>
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<author><name sortKey="Zanke, Brent W" sort="Zanke, Brent W" uniqKey="Zanke B" first="Brent W." last="Zanke">Brent W. Zanke</name>
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<author><name sortKey="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name>
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<author><name sortKey="Rangrej, Jagadish" sort="Rangrej, Jagadish" uniqKey="Rangrej J" first="Jagadish" last="Rangrej">Jagadish Rangrej</name>
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<author><name sortKey="Vijayaraghavan, Raakhee" sort="Vijayaraghavan, Raakhee" uniqKey="Vijayaraghavan R" first="Raakhee" last="Vijayaraghavan">Raakhee Vijayaraghavan</name>
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<author><name sortKey="Chan, Andrew T" sort="Chan, Andrew T" uniqKey="Chan A" first="Andrew T." last="Chan">Andrew T. Chan</name>
<affiliation><nlm:aff id="A10">Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<author><name sortKey="Hazra, Aditi" sort="Hazra, Aditi" uniqKey="Hazra A" first="Aditi" last="Hazra">Aditi Hazra</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<affiliation><nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
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<author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J." last="Hunter">David J. Hunter</name>
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<author><name sortKey="Ma, Jing" sort="Ma, Jing" uniqKey="Ma J" first="Jing" last="Ma">Jing Ma</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<author><name sortKey="Fuchs, Charles S" sort="Fuchs, Charles S" uniqKey="Fuchs C" first="Charles S." last="Fuchs">Charles S. Fuchs</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<affiliation><nlm:aff id="A13">Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Giovannucci, Edward L" sort="Giovannucci, Edward L" uniqKey="Giovannucci E" first="Edward L." last="Giovannucci">Edward L. Giovannucci</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
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<affiliation><nlm:aff id="A14">Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</nlm:aff>
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<author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name>
<affiliation><nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
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<author><name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name>
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<author><name sortKey="Chen, Lin" sort="Chen, Lin" uniqKey="Chen L" first="Lin" last="Chen">Lin Chen</name>
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<author><name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name>
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<author><name sortKey="Makar, Karen W" sort="Makar, Karen W" uniqKey="Makar K" first="Karen W." last="Makar">Karen W. Makar</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
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<author><name sortKey="Taverna, Darin" sort="Taverna, Darin" uniqKey="Taverna D" first="Darin" last="Taverna">Darin Taverna</name>
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<author><name sortKey="Gruber, Stephen B" sort="Gruber, Stephen B" uniqKey="Gruber S" first="Stephen B." last="Gruber">Stephen B. Gruber</name>
<affiliation><nlm:aff id="A17">Department of Internal Medicine, University of Michigan, Ann Arbor, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name>
<affiliation><nlm:aff id="A18">Department of Community Medicine and Epidemiology, CarmelMedical Center and Technion Faculty of Medicine, Haifa, Israel</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moreno, Victor" sort="Moreno, Victor" uniqKey="Moreno V" first="Victor" last="Moreno">Victor Moreno</name>
<affiliation><nlm:aff id="A19">Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain</nlm:aff>
</affiliation>
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<author><name sortKey="Ulrich, Cornelia M" sort="Ulrich, Cornelia M" uniqKey="Ulrich C" first="Cornelia M." last="Ulrich">Cornelia M. Ulrich</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A20">Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</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><nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A22">Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kooperberg, Charles" sort="Kooperberg, Charles" uniqKey="Kooperberg C" first="Charles" last="Kooperberg">Charles Kooperberg</name>
<affiliation><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</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><nlm:aff id="A24">Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, USA</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</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><nlm:aff id="A25">Division of Research, Kaiser Permanente Medical Care Program, Oakland, USA</nlm:aff>
</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><nlm:aff id="A26">Division of Epidemiology, Department of Environmental Medicine, New YorkUniversity School of Medicine, New York City, USA</nlm:aff>
</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><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>
</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><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>
</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><nlm:aff id="A28">Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, USA</nlm:aff>
</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><nlm:aff id="A29">Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Frank, Bernd" sort="Frank, Bernd" uniqKey="Frank B" first="Bernd" last="Frank">Bernd Frank</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name>
<affiliation><nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
<affiliation><nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
</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><nlm:aff id="A32">Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, USA</nlm:aff>
</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><nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
</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><nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
</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><nlm:aff id="A34">Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu, USA</nlm:aff>
</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><nlm:aff id="A35">Department of Medical Genetics, Mayo Clinic, Rochester, USA</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<affiliation><nlm:aff id="A36">Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, USA</nlm:aff>
</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><nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A37">Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</nlm:aff>
</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><nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
</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><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Casey, Graham" sort="Casey, Graham" uniqKey="Casey G" first="Graham" last="Casey">Graham Casey</name>
<affiliation><nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
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<date when="2011">2011</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk</title>
<author><name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hutter, Carolyn M" sort="Hutter, Carolyn M" uniqKey="Hutter C" first="Carolyn M." last="Hutter">Carolyn M. Hutter</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name>
<affiliation><nlm:aff id="A3">Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schumacher, Fredrick R" sort="Schumacher, Fredrick R" uniqKey="Schumacher F" first="Fredrick R." last="Schumacher">Fredrick R. Schumacher</name>
<affiliation><nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Conti, David V" sort="Conti, David V" uniqKey="Conti D" first="David V." last="Conti">David V. Conti</name>
<affiliation><nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carlson, Christopher S" sort="Carlson, Christopher S" uniqKey="Carlson C" first="Christopher S." last="Carlson">Christopher S. Carlson</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Edlund, Christopher K" sort="Edlund, Christopher K" uniqKey="Edlund C" first="Christopher K." last="Edlund">Christopher K. Edlund</name>
<affiliation><nlm:aff id="A5">Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</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><nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name>
<affiliation><nlm:aff id="A6">Department of Surgery, University Health Network, Toronto General Hospital, Toronto, Canada</nlm:aff>
</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><nlm:aff id="A7">Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lemire, Mathieu" sort="Lemire, Mathieu" uniqKey="Lemire M" first="Mathieu" last="Lemire">Mathieu Lemire</name>
<affiliation><nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rangrej, Jagadish" sort="Rangrej, Jagadish" uniqKey="Rangrej J" first="Jagadish" last="Rangrej">Jagadish Rangrej</name>
<affiliation><nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Vijayaraghavan, Raakhee" sort="Vijayaraghavan, Raakhee" uniqKey="Vijayaraghavan R" first="Raakhee" last="Vijayaraghavan">Raakhee Vijayaraghavan</name>
<affiliation><nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
</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><nlm:aff id="A10">Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hazra, Aditi" sort="Hazra, Aditi" uniqKey="Hazra A" first="Aditi" last="Hazra">Aditi Hazra</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
</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><nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ma, Jing" sort="Ma, Jing" uniqKey="Ma J" first="Jing" last="Ma">Jing Ma</name>
<affiliation><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</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><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A13">Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA</nlm:aff>
</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><nlm:aff id="A11">Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A14">Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name>
<affiliation><nlm:aff id="A12">Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liu, Yan" sort="Liu, Yan" uniqKey="Liu Y" first="Yan" last="Liu">Yan Liu</name>
<affiliation><nlm:aff id="A15">Quantitative Services, Baylor Health Care System, Dallas, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chen, Lin" sort="Chen, Lin" uniqKey="Chen L" first="Lin" last="Chen">Lin Chen</name>
<affiliation><nlm:aff id="A16">Department of Health Studies, University of Chicago, Chicago, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jiao, Shuo" sort="Jiao, Shuo" uniqKey="Jiao S" first="Shuo" last="Jiao">Shuo Jiao</name>
<affiliation><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Taverna, Darin" sort="Taverna, Darin" uniqKey="Taverna D" first="Darin" last="Taverna">Darin Taverna</name>
<affiliation><nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
</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><nlm:aff id="A17">Department of Internal Medicine, University of Michigan, Ann Arbor, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name>
<affiliation><nlm:aff id="A18">Department of Community Medicine and Epidemiology, CarmelMedical Center and Technion Faculty of Medicine, Haifa, Israel</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moreno, Victor" sort="Moreno, Victor" uniqKey="Moreno V" first="Victor" last="Moreno">Victor Moreno</name>
<affiliation><nlm:aff id="A19">Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A20">Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</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><nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A21">Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A22">Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</nlm:aff>
</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><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kooperberg, Charles" sort="Kooperberg, Charles" uniqKey="Kooperberg C" first="Charles" last="Kooperberg">Charles Kooperberg</name>
<affiliation><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</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><nlm:aff id="A24">Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, USA</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</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><nlm:aff id="A25">Division of Research, Kaiser Permanente Medical Care Program, Oakland, USA</nlm:aff>
</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><nlm:aff id="A26">Division of Epidemiology, Department of Environmental Medicine, New YorkUniversity School of Medicine, New York City, USA</nlm:aff>
</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><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>
</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><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>
</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><nlm:aff id="A28">Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, USA</nlm:aff>
</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><nlm:aff id="A29">Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hoffmeister, Michael" sort="Hoffmeister, Michael" uniqKey="Hoffmeister M" first="Michael" last="Hoffmeister">Michael Hoffmeister</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brenner, Hermann" sort="Brenner, Hermann" uniqKey="Brenner H" first="Hermann" last="Brenner">Hermann Brenner</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Frank, Bernd" sort="Frank, Bernd" uniqKey="Frank B" first="Bernd" last="Frank">Bernd Frank</name>
<affiliation><nlm:aff id="A30">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bezieau, Stephane" sort="Bezieau, Stephane" uniqKey="Bezieau S" first="Stéphane" last="Bézieau">Stéphane Bézieau</name>
<affiliation><nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kury, Sebastien" sort="Kury, Sebastien" uniqKey="Kury S" first="Sébastien" last="Küry">Sébastien Küry</name>
<affiliation><nlm:aff id="A31">Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</nlm:aff>
</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><nlm:aff id="A32">Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, USA</nlm:aff>
</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><nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
</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><nlm:aff id="A33">Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</nlm:aff>
</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><nlm:aff id="A34">Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu, USA</nlm:aff>
</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><nlm:aff id="A35">Department of Medical Genetics, Mayo Clinic, Rochester, USA</nlm:aff>
</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><nlm:aff id="A1">Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<affiliation><nlm:aff id="A36">Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, USA</nlm:aff>
</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><nlm:aff id="A8">Ontario Institute for Cancer Research, Toronto, Canada</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A37">Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</nlm:aff>
</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><nlm:aff id="A9">Translational Genomics Research Institute, Phoenix, USA</nlm:aff>
</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><nlm:aff id="A2">Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A23">Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Casey, Graham" sort="Casey, Graham" uniqKey="Casey G" first="Graham" last="Casey">Graham Casey</name>
<affiliation><nlm:aff id="A4">Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</nlm:aff>
</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>
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<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>
<pmc article-type="research-article" xml:lang="en"><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-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">21761138</article-id>
<article-id pub-id-type="pmc">3257356</article-id>
<article-id pub-id-type="doi">10.1007/s00439-011-1055-0</article-id>
<article-id pub-id-type="manuscript">NIHMS324653</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Peters</surname>
<given-names>Ulrike</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="FN2" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hutter</surname>
<given-names>Carolyn M.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="FN2" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hsu</surname>
<given-names>Li</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schumacher</surname>
<given-names>Fredrick R.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Conti</surname>
<given-names>David V.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Carlson</surname>
<given-names>Christopher S.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Edlund</surname>
<given-names>Christopher K.</given-names>
</name>
<xref rid="A5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haile</surname>
<given-names>Robert W.</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gallinger</surname>
<given-names>Steven</given-names>
</name>
<xref rid="A6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zanke</surname>
<given-names>Brent W.</given-names>
</name>
<xref rid="A7" ref-type="aff">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lemire</surname>
<given-names>Mathieu</given-names>
</name>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rangrej</surname>
<given-names>Jagadish</given-names>
</name>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vijayaraghavan</surname>
<given-names>Raakhee</given-names>
</name>
<xref rid="A9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chan</surname>
<given-names>Andrew T.</given-names>
</name>
<xref rid="A10" ref-type="aff">10</xref>
<xref rid="A11" ref-type="aff">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hazra</surname>
<given-names>Aditi</given-names>
</name>
<xref rid="A11" ref-type="aff">11</xref>
<xref rid="A12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hunter</surname>
<given-names>David J.</given-names>
</name>
<xref rid="A12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Jing</given-names>
</name>
<xref rid="A11" ref-type="aff">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fuchs</surname>
<given-names>Charles S.</given-names>
</name>
<xref rid="A11" ref-type="aff">11</xref>
<xref rid="A13" ref-type="aff">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Giovannucci</surname>
<given-names>Edward L.</given-names>
</name>
<xref rid="A11" ref-type="aff">11</xref>
<xref rid="A14" ref-type="aff">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kraft</surname>
<given-names>Peter</given-names>
</name>
<xref rid="A12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liu</surname>
<given-names>Yan</given-names>
</name>
<xref rid="A15" ref-type="aff">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chen</surname>
<given-names>Lin</given-names>
</name>
<xref rid="A16" ref-type="aff">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jiao</surname>
<given-names>Shuo</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Makar</surname>
<given-names>Karen W.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taverna</surname>
<given-names>Darin</given-names>
</name>
<xref rid="A9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gruber</surname>
<given-names>Stephen B.</given-names>
</name>
<xref rid="A17" ref-type="aff">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rennert</surname>
<given-names>Gad</given-names>
</name>
<xref rid="A18" ref-type="aff">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moreno</surname>
<given-names>Victor</given-names>
</name>
<xref rid="A19" ref-type="aff">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ulrich</surname>
<given-names>Cornelia M.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
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</contrib>
<contrib contrib-type="author"><name><surname>Woods</surname>
<given-names>Michael O.</given-names>
</name>
<xref rid="A21" ref-type="aff">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Green</surname>
<given-names>Roger C.</given-names>
</name>
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</contrib>
<contrib contrib-type="author"><name><surname>Parfrey</surname>
<given-names>Patrick S.</given-names>
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</contrib>
<contrib contrib-type="author"><name><surname>Prentice</surname>
<given-names>Ross L.</given-names>
</name>
<xref rid="A23" ref-type="aff">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kooperberg</surname>
<given-names>Charles</given-names>
</name>
<xref rid="A23" ref-type="aff">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jackson</surname>
<given-names>Rebecca D.</given-names>
</name>
<xref rid="A24" ref-type="aff">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>LaCroix</surname>
<given-names>Andrea Z.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Caan</surname>
<given-names>Bette J.</given-names>
</name>
<xref rid="A25" ref-type="aff">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hayes</surname>
<given-names>Richard B.</given-names>
</name>
<xref rid="A26" ref-type="aff">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Berndt</surname>
<given-names>Sonja I.</given-names>
</name>
<xref rid="A27" ref-type="aff">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chanock</surname>
<given-names>Stephen J.</given-names>
</name>
<xref rid="A27" ref-type="aff">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schoen</surname>
<given-names>Robert E.</given-names>
</name>
<xref rid="A28" ref-type="aff">28</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chang-Claude</surname>
<given-names>Jenny</given-names>
</name>
<xref rid="A29" ref-type="aff">29</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hoffmeister</surname>
<given-names>Michael</given-names>
</name>
<xref rid="A30" ref-type="aff">30</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brenner</surname>
<given-names>Hermann</given-names>
</name>
<xref rid="A30" ref-type="aff">30</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Frank</surname>
<given-names>Bernd</given-names>
</name>
<xref rid="A30" ref-type="aff">30</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bézieau</surname>
<given-names>Stéphane</given-names>
</name>
<xref rid="A31" ref-type="aff">31</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Küry</surname>
<given-names>Sébastien</given-names>
</name>
<xref rid="A31" ref-type="aff">31</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Slattery</surname>
<given-names>Martha L.</given-names>
</name>
<xref rid="A32" ref-type="aff">32</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hopper</surname>
<given-names>John L.</given-names>
</name>
<xref rid="A33" ref-type="aff">33</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jenkins</surname>
<given-names>Mark A.</given-names>
</name>
<xref rid="A33" ref-type="aff">33</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Le Marchand</surname>
<given-names>Loic</given-names>
</name>
<xref rid="A34" ref-type="aff">34</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lindor</surname>
<given-names>Noralane M.</given-names>
</name>
<xref rid="A35" ref-type="aff">35</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Newcomb</surname>
<given-names>Polly A.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Seminara</surname>
<given-names>Daniela</given-names>
</name>
<xref rid="A36" ref-type="aff">36</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hudson</surname>
<given-names>Thomas J.</given-names>
</name>
<xref rid="A8" ref-type="aff">8</xref>
<xref rid="A37" ref-type="aff">37</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Duggan</surname>
<given-names>David J.</given-names>
</name>
<xref rid="A9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Potter</surname>
<given-names>John D.</given-names>
</name>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="A23" ref-type="aff">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Casey</surname>
<given-names>Graham</given-names>
</name>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<on-behalf-of>on behalf of CCFR</on-behalf-of>
<xref rid="A38" ref-type="aff">38</xref>
<on-behalf-of>GECCO</on-behalf-of>
<xref rid="A39" ref-type="aff">39</xref>
</contrib-group>
<aff id="A1"><label>1</label>
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA</aff>
<aff id="A2"><label>2</label>
Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA</aff>
<aff id="A3"><label>3</label>
Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, USA</aff>
<aff id="A4"><label>4</label>
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA</aff>
<aff id="A5"><label>5</label>
Keck School of Medicine, University of Southern California, Los Angeles, USA</aff>
<aff id="A6"><label>6</label>
Department of Surgery, University Health Network, Toronto General Hospital, Toronto, Canada</aff>
<aff id="A7"><label>7</label>
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada</aff>
<aff id="A8"><label>8</label>
Ontario Institute for Cancer Research, Toronto, Canada</aff>
<aff id="A9"><label>9</label>
Translational Genomics Research Institute, Phoenix, USA</aff>
<aff id="A10"><label>10</label>
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, USA</aff>
<aff id="A11"><label>11</label>
Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA</aff>
<aff id="A12"><label>12</label>
Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, USA</aff>
<aff id="A13"><label>13</label>
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, USA</aff>
<aff id="A14"><label>14</label>
Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, USA</aff>
<aff id="A15"><label>15</label>
Quantitative Services, Baylor Health Care System, Dallas, USA</aff>
<aff id="A16"><label>16</label>
Department of Health Studies, University of Chicago, Chicago, USA</aff>
<aff id="A17"><label>17</label>
Department of Internal Medicine, University of Michigan, Ann Arbor, USA</aff>
<aff id="A18"><label>18</label>
Department of Community Medicine and Epidemiology, CarmelMedical Center and Technion Faculty of Medicine, Haifa, Israel</aff>
<aff id="A19"><label>19</label>
Biostatistics and Bioinformatics Unit, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain</aff>
<aff id="A20"><label>20</label>
Division of Preventive Oncology, German Cancer Research Center, Heidelberg, Germany</aff>
<aff id="A21"><label>21</label>
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</aff>
<aff id="A22"><label>22</label>
Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada</aff>
<aff id="A23"><label>23</label>
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA</aff>
<aff id="A24"><label>24</label>
Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, USA</aff>
<aff id="A25"><label>25</label>
Division of Research, Kaiser Permanente Medical Care Program, Oakland, USA</aff>
<aff id="A26"><label>26</label>
Division of Epidemiology, Department of Environmental Medicine, New YorkUniversity School of Medicine, New York City, USA</aff>
<aff id="A27"><label>27</label>
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, USA</aff>
<aff id="A28"><label>28</label>
Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, USA</aff>
<aff id="A29"><label>29</label>
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany</aff>
<aff id="A30"><label>30</label>
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany</aff>
<aff id="A31"><label>31</label>
Centre Hospitalier Universitaire (CHU) de Nantes, Pôle de Biologie, Service de Génétique Médicale, Nantes, France</aff>
<aff id="A32"><label>32</label>
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, USA</aff>
<aff id="A33"><label>33</label>
Centre for Molecular, Environmental, Genetic, and Analytical Epidemiology, University of Melbourne, Melbourne, Australia</aff>
<aff id="A34"><label>34</label>
Epidemiology Program, Cancer Research Center of Hawai’i, University of Hawai’i at Manoa, Honolulu, USA</aff>
<aff id="A35"><label>35</label>
Department of Medical Genetics, Mayo Clinic, Rochester, USA</aff>
<aff id="A36"><label>36</label>
Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, USA</aff>
<aff id="A37"><label>37</label>
Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, Canada</aff>
<aff id="A38"><label>38</label>
CCFR: Colon Cancer Family Registry</aff>
<aff id="A39"><label>39</label>
GECCO: Genetics and Epidemiology of Colorectal Cancer Consortium</aff>
<author-notes><corresp id="FN1">Correspondence should be addressed to both: Ulrike Peters, <email>upeters@fhcrc.org</email>
, Tel: +1 (206) 667-2450. Graham Casey, <email>gcasey@usc.edu</email>
, Tel: +1 (323) 442-7865</corresp>
<fn id="FN2"><label>*</label>
<p>The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>26</day>
<month>9</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>7</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>2</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>2</month>
<year>2013</year>
</pub-date>
<volume>131</volume>
<issue>2</issue>
<fpage>217</fpage>
<lpage>234</lpage>
<abstract><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>
</abstract>
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</front>
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