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A novel colorectal cancer risk locus at 4q32.2 identified from an international genome-wide association study.
Schmit, Stephanie L; Schumacher, Fredrick R; Edlund, Christopher K; Conti, David V; Raskin, Leon; Lejbkowicz, Flavio; Pinchev, Mila; Rennert, Hedy S; Jenkins, Mark A; Hopper, John L; Buchanan, Daniel D; Lindor, Noralane M; Le Marchand, Loic; Gallinger, Steven; Haile, Robert W; Newcomb, Polly A; Huang, Shu-Chen; Rennert, Gad; Casey, Graham; Gruber, Stephen B.
Affiliation
  • Schmit SL; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Schumacher FR; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Edlund CK; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Conti DV; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Raskin L; Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Lejbkowicz F; Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, National Cancer Control Center, Haifa, Israel.
  • Pinchev M; Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, National Cancer Control Center, Haifa, Israel.
  • Rennert HS; Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, National Cancer Control Center, Haifa, Israel.
  • Jenkins MA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
  • Hopper JL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
  • Buchanan DD; Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Victoria, Australia.
  • Lindor NM; Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, 8525 AZ, USA.
  • Le Marchand L; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
  • Gallinger S; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Haile RW; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA 94305, USA.
  • Newcomb PA; Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA and.
  • Huang SC; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Rennert G; Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, National Cancer Control Center, Haifa, Israel, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
  • Casey G; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
  • Gruber SB; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, TN 37232, USA, Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel, Clalit Health Services, Nat
Carcinogenesis ; 35(11): 2512-9, 2014 Nov.
Article in En | MEDLINE | ID: mdl-25023989
ABSTRACT
Only a fraction of colorectal cancer heritability is explained by known risk-conferring genetic variation. This study was designed to identify novel risk alleles in Europeans. We conducted a genome-wide association study (GWAS) meta-analysis of colorectal cancer in participants from a population-based case-control study in Israel (n = 1616 cases, 1329 controls) and a consortium study from the Colon Cancer Family Registry (n = 1977 cases, 999 controls). We used a two-stage (discovery-replication) GWAS design, followed by a joint meta-analysis. A combined analysis identified a novel susceptibility locus that reached genome-wide significance on chromosome 4q32.2 [rs35509282, risk allele = A (minor allele frequency = 0.09); odds ratio (OR) per risk allele = 1.53; P value = 8.2 × 10(-9); nearest gene = FSTL5]. The direction of the association was consistent across studies. In addition, we confirmed that 14 of 29 previously identified susceptibility variants were significantly associated with risk of colorectal cancer in this study. Genetic variation on chromosome 4q32.2 is significantly associated with risk of colorectal cancer in Ashkenazi Jews and Europeans in this study.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Genetic Predisposition to Disease / Genome-Wide Association Study / Carcinogenesis Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Carcinogenesis Year: 2014 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Genetic Predisposition to Disease / Genome-Wide Association Study / Carcinogenesis Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Carcinogenesis Year: 2014 Document type: Article