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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Identification of genetic susceptibility loci for colorectal tumors in a genome-wide meta-analysis
Gastroenterology, Volume 144, No. 4, Year 2013
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Description
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 conventional genome-wide significance level at less than 5.0 × 10 -8: an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10-8). We also found evidence for 3 additional loci with P values less than 5.0 × 10-7: a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10-8), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10-8), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10 -7). Conclusions: In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation. © 2013 AGA Institute.
Authors & Co-Authors
Peters, Ulrike
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Schumacher, Fredrick R.
United States, Los Angeles
University of Southern California
Hutter, Carolyn M.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Aragaki, Aaron K.
United States, Seattle
Fred Hutchinson Cancer Center
Baron, John Anthony
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Berndt, Sonja I.
United States, Rockville
National Cancer Institute Nci
Bézieau, Stéphane
France, Nantes
Chu de Nantes
Brenner, Hermann
Germany, Heidelberg
German Cancer Research Center
Caan, Bette J.
United States, Oakland
Kaiser Permanente
Campbell, Peter T.
United States, Kennesaw
American Cancer Society
Carlson, Christopher S.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Casey, Graham R.
United States, Los Angeles
University of Southern California
Chan, Andrew Tan
United States, Boston
Harvard Medical School
Chang-Claude, Jenny C.
Germany, Heidelberg
German Cancer Research Center
Chanock, Stephen J.
United States, Rockville
National Cancer Institute Nci
Chen, Linsu
United States, Chicago
The University of Chicago
Coetzee, Gerhard A.
United States, Los Angeles
University of Southern California
Coetzee, Simon G.
United States, Los Angeles
University of Southern California
Conti, David V.
United States, Los Angeles
University of Southern California
Curtis, Keith R.
United States, Seattle
Fred Hutchinson Cancer Center
Duggan, David J.
United States, Phoenix
Translational Genomics Research Institute
Edwards, Todd L.
United States, Nashville
Vanderbilt University School of Medicine
Fuchs, Charles Stewart
United States, Boston
Harvard Medical School
United States, Boston
Dana-farber Cancer Institute
Gallinger, Steven J.
Canada, Toronto
Toronto General Hospital
Giovannucci, Edward Luciano
United States, Boston
Harvard Medical School
United States, Cambridge
Harvard University
Gogarten, Stephanie M.
United States, Seattle
University of Washington
Gruber, Stephen Bernard
United States, Los Angeles
University of Southern California
Haile, Robert W.C.
United States, Los Angeles
University of Southern California
Harrison, Tabitha A.
United States, Seattle
Fred Hutchinson Cancer Center
Hayes, Richard B.
United States, New York
New York University
Henderson, Brian E.
United States, Los Angeles
University of Southern California
Hoffmeister, Michael
Germany, Heidelberg
German Cancer Research Center
Hopper, John Llewelyn
Australia, Melbourne
University of Melbourne
Hunter, D. J.
United States, Cambridge
Harvard University
Jackson, Rebecca D.
United States, Columbus
The Ohio State University
Jee, Sunha
Unknown Affiliation
Jenkins, Mark Andrew
Australia, Melbourne
University of Melbourne
Kolonel, Laurence N.
United States, Honolulu
University of Hawaiʻi Cancer Center
Kooperberg, Charles L.
United States, Seattle
Fred Hutchinson Cancer Center
Küry, Sébastien
France, Nantes
Chu de Nantes
LaCroix, Andrea Z.
United States, Seattle
Fred Hutchinson Cancer Center
Laurie, Cathy C.
United States, Seattle
University of Washington
Laurie, Cecilia A.
United States, Seattle
University of Washington
Le Marchand, Loic̈
United States, Honolulu
University of Hawaiʻi Cancer Center
Lemire, Mathieu
Canada, Toronto
Ontario Institute for Cancer Research
Levine, David M.
United States, Seattle
University of Washington
Lindor, Noralane M.
United States, Scottsdale
Mayo Clinic Scottsdale-phoenix, Arizona
Ma, Jing
United States, Boston
Harvard Medical School
Matsuo, Keitaro
Japan, Nagoya
Aichi Cancer Center Hospital and Research Institute
Newcomb, Polly A.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Potter, John D.
United States, Seattle
Fred Hutchinson Cancer Center
New Zealand, Wellington
Massey University Wellington
Prentice, Ross L.
United States, Seattle
Fred Hutchinson Cancer Center
Qu, Conghui
United States, Seattle
Fred Hutchinson Cancer Center
Rohan, Thomas E.
United States, New York
Albert Einstein College of Medicine of Yeshiva University
Schoen, Robert E.
United States, Pittsburgh
University of Pittsburgh Medical Center
Seminara, Daniela
United States, Rockville
National Cancer Institute Nci
Shu, Xiaoou
United States, Nashville
Vanderbilt University School of Medicine
Thibodeau, Stephen N.
United States, Rochester
Mayo Clinic
Ulrich, Cornelia M.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Germany, Heidelberg
German Cancer Research Center
Xiang, Yongbing
China, Shanghai
Shanghai Cancer Institute
Zeng, Yixin
China, Guangzhou
Sun Yat-sen University
Zheng, Wei
United States, Nashville
Vanderbilt University School of Medicine
Hsu, Li
United States, Seattle
Fred Hutchinson Cancer Center
Statistics
Citations: 269
Authors: 63
Affiliations: 32
Identifiers
Doi:
10.1053/j.gastro.2012.12.020
ISSN:
00165085
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study
Study Approach
Systematic review