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A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1

Identifieur interne : 003244 ( Main/Exploration ); précédent : 003243; suivant : 003245

A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1

Auteurs : Mathieu Lemire [Canada] ; Conghui Qu [États-Unis] ; Lenora W. M. Loo [États-Unis] ; Syed H. E. Zaidi [Canada] ; Hansong Wang [États-Unis] ; Sonja I. Berndt [États-Unis] ; Stéphane Bézieau [France] ; Hermann Brenner [Allemagne] ; Peter T. Campbell [États-Unis] ; Andrew T. Chan [États-Unis] ; Jenny Chang-Claude [Allemagne] ; Mengmeng Du [États-Unis] ; Christopher K. Edlund [États-Unis] ; Steven Gallinger [Canada] ; Robert W. Haile [États-Unis] ; Tabitha A. Harrison [États-Unis] ; Michael Hoffmeister [Allemagne] ; John L. Hopper [Australie] ; Lifang Hou [États-Unis] ; Li Hsu [États-Unis] ; Eric J. Jacobs [États-Unis] ; Mark A. Jenkins [Australie] ; Jihyoun Jeon [États-Unis] ; Sébastien Küry [France] ; Li Li [États-Unis] ; Noralane M. Lindor [États-Unis] ; Polly A. Newcomb [États-Unis] ; John D. Potter [États-Unis, Nouvelle-Zélande] ; Gad Rennert [Israël] ; Anja Rudolph [Allemagne] ; Robert E. Schoen [États-Unis] ; Fredrick R. Schumacher [États-Unis] ; Daniela Seminara [États-Unis] ; Gianluca Severi [Australie, Italie] ; Martha L. Slattery [États-Unis] ; Emily White [États-Unis] ; Michael O. Woods [Canada] ; Michelle Cotterchio [Canada] ; Loic Le Marchand [États-Unis] ; Graham Casey [États-Unis] ; Steven B. Gruber [États-Unis] ; Ulrike Peters [États-Unis] ; Thomas J. Hudson [Canada]

Source :

RBID : PMC:4687971

Descripteurs français

English descriptors

Abstract

Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of CR polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC (p=2.5×10−10; odds ratio estimated by re-including all controls (OR)=0.87, 95% confidence interval (CI): 0.83–0.91; minor allele frequency (MAF)=13%). Results were replicated in samples of African descent (1,894 cases and 4,703 controls; p=0.01; OR=0.86, 95% CI: 0.77–0.97; MAF=16%). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p=0.001), a protein-coding gene involved in survival and proliferation of cancer cells that is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p=1.3×10−8).


Url:
DOI: 10.1007/s00439-015-1598-6
PubMed: 26404086
PubMed Central: 4687971


Affiliations:

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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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<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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<region type="state">Washington (État)</region>
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<wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health, Seattle</wicri:cityArea>
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<nlm:aff id="A24">Centre for Public Health Research, Massey University, Wellington, New Zealand</nlm:aff>
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<wicri:regionArea>Centre for Public Health Research, Massey University, Wellington</wicri:regionArea>
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<region type="state">Washington (État)</region>
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<nlm:aff id="A34">Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
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<wicri:regionArea>Cancer Care Ontario, University of Toronto, Toronto, Ontario</wicri:regionArea>
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<nlm:aff id="A3">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</nlm:aff>
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<region type="state">Hawaï</region>
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<wicri:regionArea>Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1</wicri:regionArea>
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<title xml:lang="en" level="a" type="main">A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1</title>
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<name sortKey="Du, Mengmeng" sort="Du, Mengmeng" uniqKey="Du M" first="Mengmeng" last="Du">Mengmeng Du</name>
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<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</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 wicri:level="4">
<nlm:aff id="A14">USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Gallinger, Steven" sort="Gallinger, Steven" uniqKey="Gallinger S" first="Steven" last="Gallinger">Steven Gallinger</name>
<affiliation wicri:level="1">
<nlm:aff id="A15">Samuel Lunenfeld Research Institute, Toronto, ON M5S 1X5, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Samuel Lunenfeld Research Institute, Toronto, ON M5S 1X5</wicri:regionArea>
<wicri:noRegion>ON M5S 1X5</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A16">Division of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Division of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4</wicri:regionArea>
<wicri:noRegion>ON M5G 2C4</wicri:noRegion>
</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="2">
<nlm:aff id="A17">Department of Medicine, Division of Oncology, Stanford University, California, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, Division of Oncology, Stanford University, California</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Harrison, Tabitha A" sort="Harrison, Tabitha A" uniqKey="Harrison T" first="Tabitha A." last="Harrison">Tabitha A. Harrison</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</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="A7">Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea>
<placeName>
<region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
<affiliation wicri:level="4">
<nlm:aff id="A18">Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Epidemiology and Biostatistics, School of Population and Global Health, The 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="Hou, Lifang" sort="Hou, Lifang" uniqKey="Hou L" first="Lifang" last="Hou">Lifang Hou</name>
<affiliation wicri:level="2">
<nlm:aff id="A19"> Department of Preventive Medicine and the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Illinois</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Illinois</region>
</placeName>
<wicri:cityArea> Department of Preventive Medicine and the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Hsu, Li" sort="Hsu, Li" uniqKey="Hsu L" first="Li" last="Hsu">Li Hsu</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A20">Department of Biostatistics, University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Biostatistics, University of Washington, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Jacobs, Eric J" sort="Jacobs, Eric J" uniqKey="Jacobs E" first="Eric J." last="Jacobs">Eric J. Jacobs</name>
<affiliation wicri:level="2">
<nlm:aff id="A10">American Cancer Society, Atlanta, GA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>American Cancer Society, Atlanta, GA</wicri:regionArea>
<placeName>
<region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name>
<affiliation wicri:level="4">
<nlm:aff id="A18">Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Epidemiology and Biostatistics, School of Population and Global Health, The 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="Jeon, Jihyoun" sort="Jeon, Jihyoun" uniqKey="Jeon J" first="Jihyoun" last="Jeon">Jihyoun Jeon</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</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="A5">Service de Génétique Médicale, CHU Nantes, Nantes, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Génétique Médicale, CHU Nantes, Nantes</wicri:regionArea>
<placeName>
<region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name>
<affiliation wicri:level="2">
<nlm:aff id="A21">Case Comprehensive Cancer Center and Swetland Center for Environmental Health, Case Western Reserve University, Cleveland, Ohio</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Ohio</region>
</placeName>
<wicri:cityArea>Case Comprehensive Cancer Center and Swetland Center for Environmental Health, Case Western Reserve University, Cleveland</wicri:cityArea>
</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="2">
<nlm:aff id="A22">Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Arizona</region>
</placeName>
<wicri:cityArea>Department of Health Sciences Research, Mayo Clinic, Scottsdale</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Newcomb, Polly A" sort="Newcomb, Polly A" uniqKey="Newcomb P" first="Polly A." last="Newcomb">Polly A. Newcomb</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A23">Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health, Seattle</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Potter, John D" sort="Potter, John D" uniqKey="Potter J" first="John D." last="Potter">John D. Potter</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A23">Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A24">Centre for Public Health Research, Massey University, Wellington, New Zealand</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Centre for Public Health Research, Massey University, Wellington</wicri:regionArea>
<wicri:noRegion>Wellington</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name>
<affiliation wicri:level="1">
<nlm:aff id="A25">Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa</wicri:regionArea>
<wicri:noRegion>Haifa</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A26">Clalit Health Services National Cancer Control Center, Haifa, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Clalit Health Services National Cancer Control Center, Haifa</wicri:regionArea>
<wicri:noRegion>Haifa</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A27">Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa</wicri:regionArea>
<wicri:noRegion>Haifa</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name>
<affiliation wicri:level="3">
<nlm:aff id="A13">Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), 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="Schoen, Robert E" sort="Schoen, Robert E" uniqKey="Schoen R" first="Robert E." last="Schoen">Robert E. Schoen</name>
<affiliation wicri:level="2">
<nlm:aff id="A28">Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA</wicri:regionArea>
<placeName>
<region type="state">Pennsylvanie</region>
</placeName>
</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 wicri:level="4">
<nlm:aff id="A14">USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Seminara, Daniela" sort="Seminara, Daniela" uniqKey="Seminara D" first="Daniela" last="Seminara">Daniela Seminara</name>
<affiliation wicri:level="2">
<nlm:aff id="A29">Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="4">
<nlm:aff id="A18">Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Epidemiology and Biostatistics, School of Population and Global Health, The 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>
<affiliation wicri:level="3">
<nlm:aff id="A30">Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne</wicri:regionArea>
<placeName>
<settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="A31">Human Genetics Foundation (HuGeF), Torino, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Human Genetics Foundation (HuGeF), Torino</wicri:regionArea>
<placeName>
<settlement type="city">Turin</settlement>
<region type="région" nuts="2">Piémont</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Slattery, Martha L" sort="Slattery, Martha L" uniqKey="Slattery M" first="Martha L." last="Slattery">Martha L. Slattery</name>
<affiliation wicri:level="2">
<nlm:aff id="A32">Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, 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, UT</wicri:regionArea>
<placeName>
<region type="state">Utah</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="White, Emily" sort="White, Emily" uniqKey="White E" first="Emily" last="White">Emily White</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A23">Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Department of Epidemiology, University of Washington School of Public Health, Seattle</wicri:cityArea>
</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="A33">Discipline of Genetics, Memorial University of Newfoundland, St. John's, NF A1B 3V6, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Discipline of Genetics, Memorial University of Newfoundland, St. John's, NF A1B 3V6</wicri:regionArea>
<wicri:noRegion>NF A1B 3V6</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cotterchio, Michelle" sort="Cotterchio, Michelle" uniqKey="Cotterchio M" first="Michelle" last="Cotterchio">Michelle Cotterchio</name>
<affiliation wicri:level="4">
<nlm:aff id="A34">Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Cancer Care Ontario, University of Toronto, Toronto, Ontario</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="Marchand, Loic Le" sort="Marchand, Loic Le" uniqKey="Marchand L" first="Loic Le" last="Marchand">Loic Le Marchand</name>
<affiliation wicri:level="2">
<nlm:aff id="A3">Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Hawaï</region>
</placeName>
<wicri:cityArea>Epidemiology Program, University of Hawaii Cancer Center, Honolulu</wicri:cityArea>
</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="A14">USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Gruber, Steven B" sort="Gruber, Steven B" uniqKey="Gruber S" first="Steven B." last="Gruber">Steven B. Gruber</name>
<affiliation wicri:level="4">
<nlm:aff id="A14">USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A35">USC Norris Comprehensive Cancer Center, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>USC Norris Comprehensive Cancer Center, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA</wicri:regionArea>
<placeName>
<region type="state">Californie</region>
<settlement type="city">Los Angeles</settlement>
</placeName>
<orgName type="university">Université de Californie du Sud</orgName>
</affiliation>
</author>
<author>
<name sortKey="Peters, Ulrike" sort="Peters, Ulrike" uniqKey="Peters U" first="Ulrike" last="Peters">Ulrike Peters</name>
<affiliation wicri:level="2">
<nlm:aff id="A2">Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A36">School of Public Health, University of Washington, Seattle, Washington</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Washington (État)</region>
</placeName>
<wicri:cityArea>School of Public Health, University of Washington, Seattle</wicri:cityArea>
</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="A1">Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Ontario Institute for Cancer Research, Toronto, ON M5G 0A3</wicri:regionArea>
<wicri:noRegion>ON M5G 0A3</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A37">Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A38">Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName>
<settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</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="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Adenocarcinoma (epidemiology)</term>
<term>Adenocarcinoma (genetics)</term>
<term>Aged</term>
<term>Case-Control Studies</term>
<term>Chromosomes, Human, Pair 14 (genetics)</term>
<term>Colorectal Neoplasms (epidemiology)</term>
<term>Colorectal Neoplasms (genetics)</term>
<term>Female</term>
<term>Gene Frequency</term>
<term>Genetic Loci</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Adénocarcinome (génétique)</term>
<term>Adénocarcinome (épidémiologie)</term>
<term>Chromosomes humains de la paire 14 (génétique)</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Fréquence d'allèle</term>
<term>Humains</term>
<term>Locus génétiques</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie</term>
<term>Sujet âgé</term>
<term>Tumeurs colorectales (génétique)</term>
<term>Tumeurs colorectales (épidémiologie)</term>
<term>Étude d'association pangénomique</term>
<term>Études cas-témoins</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>Adenocarcinoma</term>
<term>Colorectal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Adenocarcinoma</term>
<term>Chromosomes, Human, Pair 14</term>
<term>Colorectal Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Adénocarcinome</term>
<term>Chromosomes humains de la paire 14</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>Adénocarcinome</term>
<term>Tumeurs colorectales</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Aged</term>
<term>Case-Control Studies</term>
<term>Female</term>
<term>Gene Frequency</term>
<term>Genetic Loci</term>
<term>Genetic Predisposition to Disease</term>
<term>Genome-Wide Association Study</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Fréquence d'allèle</term>
<term>Humains</term>
<term>Locus génétiques</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Prédisposition génétique à une maladie</term>
<term>Sujet âgé</term>
<term>Étude d'association pangénomique</term>
<term>Études cas-témoins</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P44">Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of CR polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC (
<italic>p</italic>
=2.5×10
<sup>−10</sup>
; odds ratio estimated by re-including all controls (OR)=0.87, 95% confidence interval (CI): 0.83–0.91; minor allele frequency (MAF)=13%). Results were replicated in samples of African descent (1,894 cases and 4,703 controls;
<italic>p</italic>
=0.01; OR=0.86, 95% CI: 0.77–0.97; MAF=16%). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (
<italic>p</italic>
=0.001), a protein-coding gene involved in survival and proliferation of cancer cells that is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (
<italic>p</italic>
=1.3×10
<sup>−8</sup>
).</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Israël</li>
<li>Italie</li>
<li>Nouvelle-Zélande</li>
<li>États-Unis</li>
</country>
<region>
<li>Arizona</li>
<li>Bade-Wurtemberg</li>
<li>Californie</li>
<li>District de Karlsruhe</li>
<li>Géorgie (États-Unis)</li>
<li>Hawaï</li>
<li>Illinois</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Ohio</li>
<li>Ontario</li>
<li>Pays de la Loire</li>
<li>Pennsylvanie</li>
<li>Piémont</li>
<li>Utah</li>
<li>Victoria (État)</li>
<li>Washington (État)</li>
</region>
<settlement>
<li>Heidelberg</li>
<li>Los Angeles</li>
<li>Melbourne</li>
<li>Nantes</li>
<li>Toronto</li>
<li>Turin</li>
</settlement>
<orgName>
<li>Université de Californie du Sud</li>
<li>Université de Melbourne</li>
<li>Université de Nantes</li>
<li>Université de Toronto</li>
</orgName>
</list>
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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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</country>
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<region name="Washington (État)">
<name sortKey="Qu, Conghui" sort="Qu, Conghui" uniqKey="Qu C" first="Conghui" last="Qu">Conghui Qu</name>
</region>
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<region name="Pays de la Loire">
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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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</record>

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