Quantitative assessment of the influence of common variation rs16892766 at 8q23.3 with colorectal adenoma and cancer susceptibility.

Epidemiological studies indicate a genetic contribution to colorectal cancer (CRC) and colorectal adenoma (CRA) risk, but specific genetic variants remain unknown. Recently, genome-wide association studies have identified 8q23.3-rs16892766 as a new CRC susceptibility locus in populations of European descent. Since then, the relationship between 8q23.3-rs16892766 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 13 studies, including 41,728 patients and 44,393 controls for CRC, and 3,767 patients and 11,607 controls for CRA. An overall random-effects per-allele odds ratio of 1.19 (95 % CI: 1.13-1.25, P < 10(-5)) was found for the rs16892766 polymorphism and CRC/CRA risk. When stratified by outcome, the rs16892766 polymorphism was significantly associated with increased CRC risk with per-allele OR of 1.22 (95 % CI: 1.18-1.27, P < 10(-5)), while no associations were found for CRA (OR = 1.05, 95 % CI: 0.91-1.25, P = 0.49). In the subgroup analysis by ethnicity, significantly increased CRC risks were found among Caucasians (OR = 1.23, 95 % CI: 1.17-1.29, P < 10(-5)) and African American (OR = 1.18, 95 % CI: 1.07-1.29, P = 0.001); while no significant associations were found among other ethnic populations. Similar results were also observed under dominant and recessive genetic models. Ethnicity was identified as a potential source of between-study heterogeneity for rs16892766. When stratified by sample size and study design, significantly increased CRC risks were found for the polymorphism in all genetic models. Our findings demonstrated that rs16892766-C allele might be risk-conferring factors for the development of CRC, but not for CRA.