Meta-analysis of new genome-wide association studies of colorectal cancer risk.

Peters, Ulrike and Hutter, Carolyn M and Hsu, Li and Schumacher, Fredrick R and Conti, David V and Carlson, Christopher S and Edlund, Christopher K and Haile, Robert W and Gallinger, Steven and Zanke, Brent W and Lemire, Mathieu and Rangrej, Jagadish and Vijayaraghavan, Raakhee and Chan, Andrew T and Hazra, Aditi and Hunter, David J and Ma, Jing and Fuchs, Charles S and Giovannucci, Edward L and Kraft, Peter and Liu, Yan and Chen, Lin and Jiao, Shuo and Makar, Karen W and Taverna, Darin and Gruber, Stephen B and Rennert, Gad and Moreno, Victor and Ulrich, Cornelia M and Woods, Michael O and Green, Roger C and Parfrey, Patrick S and Prentice, Ross L and Kooperberg, Charles and Jackson, Rebecca D and Lacroix, Andrea Z and Caan, Bette J and Hayes, Richard B and Berndt, Sonja I and Chanock, Stephen J and Schoen, Robert E and Chang-Claude, Jenny and Hoffmeister, Michael and Brenner, Hermann and Frank, Bernd and Bézieau, Stéphane and Küry, Sébastien and Slattery, Martha L and Hopper, John L and Jenkins, Mark A and Le Marchand, Loic and Lindor, Noralane M and Newcomb, Polly A and Seminara, Daniela and Hudson, Thomas J and Duggan, David J and Potter, John D and Casey, Graham (2011) Meta-analysis of new genome-wide association studies of colorectal cancer risk. Human genetics. ISSN 1432-1203 (In Press)

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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.

Item Type:	Article or Abstract
Additional Information:	The final publication is available at www.springerlink.com
DOI:	10.1007/s00439-011-1055-0
PubMed ID:	21761138
NIHMSID:	NIHMS324653
Subjects:	Diseases > Solid tumors > Digestive system cancer
Depositing User:	Library Staff
Date Deposited:	13 Sep 2011 17:55
Last Modified:	14 Feb 2012 14:44
URI:	http://authors.fhcrc.org/id/eprint/498

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