Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-wide Meta-analysis
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Author
Peters, Ulrike
Jiao, Shuo
Schumacher, Fredrick R.
Hutter, Carolyn M.
Aragaki, Aaron K.
Baron, John A.
Berndt, Sonja I.
Bézieau, Stéphane
Brenner, Hermann
Butterbach, Katja
Caan, Bette J.
Campbell, Peter T.
Carlson, Christopher S.
Casey, Graham
Chan, Andrew T.
Chang-Claude, Jenny
Chanock, Stephen J.
Chen, Lin S.
Coetzee, Gerhard A.
Coetzee, Simon G.
Conti, David V.
Curtis, Keith R.
Duggan, David
Edwards, Todd
Fuchs, Charles S.
Gallinger, Steven
Giovannucci, Edward L.
Gogarten, Stephanie M.
Gruber, Stephen B.
Haile, Robert W.
Harrison, Tabitha A.
Hayes, Richard B.
Henderson, Brian E.
Hoffmeister, Michael
Hopper, John L.
Hudson, Thomas J.
Hunter, David J.
Jackson, Rebecca D.
Jee, Sun Ha
Jenkins, Mark A.
Jia, Wei-Hua
Kolonel, Laurence N.
Kooperberg, Charles
Küry, Sébastien
Lacroix, Andrea Z.
Laurie, Cathy C.
Laurie, Cecelia A.
Marchand, Loic Le
Lemire, Mathieu
Levine, David
Lindor, Noralane M.
Liu, Yan
Ma, Jing
Makar, Karen W.
Matsuo, Keitaro
Newcomb, Polly A.
Potter, John D.
Prentice, Ross L.
Qu, Conghui
Rohan, Thomas
Rosse, Stephanie A.
Schoen, Robert E.
Seminara, Daniela
Shrubsole, Martha
Shu, Xiao-Ou
Slattery, Martha L.
Taverna, Darin
Thibodeau, Stephen N.
Ulrich, Cornelia M.
White, Emily
Xiang, Yongbing
Zanke, Brent W.
Zeng, Yi-Xin
Zhang, Ben
Zheng, Wei
Hsu, Li
Published Version
https://doi.org/10.1053/j.gastro.2012.12.020Metadata
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Peters, Ulrike, Shuo Jiao, Fredrick R. Schumacher, Carolyn M. Hutter, Aaron K. Aragaki, John A. Baron, Sonja I. Berndt, et al. 2013. “Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-Analysis.” Gastroenterology 144 (4): 799–807.e24. https://doi.org/10.1053/j.gastro.2012.12.020.Abstract
BACKGROUND and 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 X 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 X 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 X 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 X 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 X 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 X 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 beta-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.Terms of Use
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