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Meta-analysis of new genome-wide association studies of colorectal cancer risk
Authors:Peters Ulrike  Hutter Carolyn M  Hsu Li  Schumacher Fredrick R  Conti David V  Carlson Christopher S  Edlund Christopher K  Haile Robert W  Gallinger Steven  Zanke Brent W  Lemire Mathieu  Rangrej Jagadish  Vijayaraghavan Raakhee  Chan Andrew T  Hazra Aditi  Hunter David J  Ma Jing  Fuchs Charles S  Giovannucci Edward L  Kraft Peter  Liu Yan  Chen Lin  Jiao Shuo  Makar Karen W  Taverna Darin  Gruber Stephen B  Rennert Gad  Moreno Victor  Ulrich Cornelia M  Woods Michael O  Green Roger C  Parfrey Patrick S  Prentice Ross L  Kooperberg Charles  Jackson Rebecca D  Lacroix Andrea Z  Caan Bette J  Hayes Richard B  Berndt Sonja I
Affiliation:Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, USA. upeters@fhcrc.org
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?
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