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 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:
|
Authors | Ulrike Peters, Shuo Jiao, Fredrick R Schumacher, Carolyn M Hutter, Aaron K Aragaki, John A Baron, Sonja I Berndt, Stéphane Bézieau, Hermann Brenner, Katja Butterbach, Bette J Caan, Peter T Campbell, Christopher S Carlson, Graham Casey, Andrew T Chan, Jenny Chang-Claude, Stephen J Chanock, Lin S Chen, Gerhard A Coetzee, Simon G Coetzee, David V Conti, Keith R Curtis, David Duggan, Todd Edwards, Charles S Fuchs, Steven Gallinger, Edward L Giovannucci, Stephanie M Gogarten, Stephen B Gruber, Robert W Haile, Tabitha A Harrison, Richard B Hayes, Brian E Henderson, Michael Hoffmeister, John L Hopper, Thomas J Hudson, David J Hunter, Rebecca D Jackson, Sun Ha Jee, Mark A Jenkins, Wei-Hua Jia, Laurence N Kolonel, Charles Kooperberg, Sébastien Küry, Andrea Z Lacroix, Cathy C Laurie, Cecelia A Laurie, Loic Le Marchand, Mathieu Lemire, David Levine, Noralane M Lindor, Yan Liu, Jing Ma, Karen W Makar, Keitaro Matsuo, Polly A Newcomb, John D Potter, Ross L Prentice, Conghui Qu, Thomas Rohan, Stephanie A Rosse, Robert E Schoen, Daniela Seminara, Martha Shrubsole, Xiao-Ou Shu, Martha L Slattery, Darin Taverna, Stephen N Thibodeau, Cornelia M Ulrich, Emily White, Yongbing Xiang, Brent W Zanke, Yi-Xin Zeng, Ben Zhang, Wei Zheng, Li Hsu, Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium |
Journal | Gastroenterology
(Gastroenterology)
Vol. 144
Issue 4
Pg. 799-807.e24
(Apr 2013)
ISSN: 1528-0012 [Electronic] United States |
PMID | 23266556
(Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
|
Copyright | Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- CCND2 protein, human
- Cyclin D2
- DNA-Binding Proteins
- Laminin
- T-Box Domain Proteins
- TBX3 protein, human
- laminin gamma 1
|
Topics |
- Age Distribution
- Aged
- Aged, 80 and over
- Colorectal Neoplasms
(epidemiology, genetics)
- Cyclin D2
(genetics)
- DNA-Binding Proteins
(genetics)
- Female
- Genetic Loci
(genetics)
- Genetic Predisposition to Disease
(epidemiology)
- Genome-Wide Association Study
- Humans
- Incidence
- Laminin
(genetics)
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Prognosis
- Risk Assessment
- Sex Distribution
- T-Box Domain Proteins
(genetics)
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|