| Literature DB >> 21761138 |
Ulrike Peters1, Carolyn M Hutter, Li Hsu, Fredrick R Schumacher, David V Conti, Christopher S Carlson, Christopher K Edlund, Robert W Haile, Steven Gallinger, Brent W Zanke, Mathieu Lemire, Jagadish Rangrej, Raakhee Vijayaraghavan, Andrew T Chan, Aditi Hazra, David J Hunter, Jing Ma, Charles S Fuchs, Edward L Giovannucci, Peter Kraft, Yan Liu, Lin Chen, Shuo Jiao, Karen W Makar, Darin Taverna, Stephen B Gruber, Gad Rennert, Victor Moreno, Cornelia M Ulrich, Michael O Woods, Roger C Green, Patrick S Parfrey, Ross L Prentice, Charles Kooperberg, Rebecca D Jackson, Andrea Z Lacroix, Bette J Caan, Richard B Hayes, Sonja I Berndt, Stephen J Chanock, Robert E Schoen, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Bernd Frank, Stéphane Bézieau, Sébastien Küry, Martha L Slattery, John L Hopper, Mark A Jenkins, Loic Le Marchand, Noralane M Lindor, Polly A Newcomb, Daniela Seminara, Thomas J Hudson, David J Duggan, John D Potter, Graham Casey.
Abstract
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.Entities:
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Year: 2011 PMID： 21761138 PMCID： PMC3257356 DOI： 10.1007/s00439-011-1055-0
Source DB: PubMed Journal: Hum Genet ISSN： 0340-6717 Impact factor: 4.132