Journal article
Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis
U Peters, S Jiao, FR Schumacher, CM Hutter, AK Aragaki, JA Baron, SI Berndt, S Bézieau, H Brenner, K Butterbach, BJ Caan, PT Campbell, CS Carlson, G Casey, AT Chan, J Chang-Claude, SJ Chanock, LS Chen, GA Coetzee, SG Coetzee Show all
Gastroenterology | Published : 2013
Abstract
Background & Aims: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. Methods: We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. Results: Based on the combined analysis, we identified a locus that reached the conven..
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Funding Acknowledgements
The Genetics and Epidemiology of Colorectal Cancer Consortium study was supported by the National Cancer Institute, National Institutes of Health, and the US Department of Health and Human Services (U01 CA137088; R01 CA059045). The Asian Consortium was supported by a Grant-in-aid for Cancer Research, the Grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (17015018 and 221S0001). The french Association STudy Evaluating RISK for sporadic colorectal cancer was supported by a Hospital Clinical Research Program (PHRC) and by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte Contre le Cancer, the Association Anne de Bretagne Genetique, and the Ligue Regionale Contre le Cancer. The Assessment of Risk in Colorectal Tumours in Canada study was supported by the National Institutes of Health through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783; see the Colon Cancer Family Registry support section below); and by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, by a Cancer Risk Evaluation Program grant from the Canadian Cancer Society Research Institute, and by Senior Investigator Awards (T.J.H. and B.W.Z.) from the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Economic Development and Innovation. The Hawaii Colorectal Cancer Studies 2 and 3 studies were supported by the National Institutes of Health (R01 CA60987). The Colon Cancer Family Registry was supported by the National Institutes of Health (RFA CA-95-011) and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. This genome-wide scan was supported by the National Cancer Institute, National Institutes of Health (U01 CA122839). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the cancer family registries, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the cancer family registries. The following colon cancer family registries centers contributed data to this article and were supported by National Institutes of Health: the Australasian Colorectal Cancer Family Registry (U01 CA097735), Seattle Colorectal Cancer Family Registry (U01 CA074794), and the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). The Darmkrebs: Chancen der Verhutung durch Screening study was supported by the German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). The Diet, Activity, and Lifestyle Study was supported by the National Institutes of Health (R01 CA48998 to M. L. S.); Guangzhou-1 was supported by the National Key Scientific and Technological Project (2011ZX09307-001-04) and the National Basic Research Program (2011CB504303) was supported by the People's Republic of China. The Health Professionals Follow-up Study was supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, and P50 CA 127003), the Nurses' Health Study was supported by the National Institutes of Health (R01 137178, P01 CA 087969, and P50 CA 127003), and the Physicians' Health Study was supported by the National Institutes of Health (CA42182). The Korean Cancer Prevention Study-II study was supported by the National R&D Program for cancer control (1220180), and the Seoul R&D Program (10526, Republic of Korea). The Multiethnic Cohort study was supported by the National Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464). The Prostate, Lung, Colorectal Cancer, and Ovarian Cancer Screening Trial was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility prostate cancer scan, supported by the Intramural Research Program of the National Cancer Institute. The data sets used in this analysis were accessed with appropriate approval through the dbGaP online resource (http://www.cgems.cancer.gov/data_acess.html) through dbGaP accession number 000207v.1p1. Control samples also were genotyped as part of the GWAS of Lung Cancer and Smoking (Yeager, M et al. Nat Genet 2008;124:161-170). Support for this work was provided through the National Institutes of Health, Genes, Environment and Health Initiative (Z01 CP 010200). The human subjects participating in the genome-wide association study were derived from the Prostate, Lung, Colon, and Ovarian Screening Trial and the study was supported by intramural resources of the National Cancer Institute. Assistance with genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies, Geneva Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the National Institutes of Health, Genes, Environment and Health Initiative (U01 HG 004438). The data sets used for the analyses described in this article were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000093 v2.p2. The Postmenopausal Hormone Study was supported by the National Institutes of Health (R01 CA076366 to P.A.N.). The Shanghai-1 and Shanghai-2 studies were supported by the National Institutes of Health (R37CA070867, R01CA082729, R01CA124558, R01CA148667, and R01CA122364), as well as an Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. The Tennessee Colorectal Polyp Study was supported by the National Institutes of Health (P50CA95103 and R01CA121060) and was conducted by the Survey and Biospecimen Shared Resource, which was supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA 68485). The VITamins And Lifestyle study was supported by the National Institutes of Health (K05 CA154337). The Women's Health Initiative program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.