Common Variation Rs6983267 at 8q24.1 and Risk of Colorectal Adenoma and Cancer: Evidence Based on 31 Studies

Genome-wide association studies have identified 8q24.21-rs6983267 as a new colorectal cancer (CRC) and colorectal adenoma (CRA) susceptibility locus in populations of European descent. Since then, the relationship between 8q24.21-rs6983267 and CRC/CRA has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a meta-analysis of 31 studies, including 51,293 cases and 58,962 controls for CRC, and 8,148 cases and 17,065 controls for CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio of G variant for CRC was 1.18 (95 % CI, 1.16-1.21; P < 10(-5)) and 1.17 (95 % CI, 1.11-1.23; P < 10(-5)) for CRA. Significant results were observed using dominant or recessive genetic model for the polymorphism. In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians and Caucasian populations; while no significant associations were detected among African Americans. After stratifying by sample size and control source, significant associations were also obtained. This meta-analysis suggests that the 8q24.21-rs6983267 polymorphism is associated with CRC/CRA susceptibility, but these associations vary in different ethnic populations.