APC Polymorphisms and the Risk of Colorectal Neoplasia: A HuGE Review and Meta-Analysis

Adenomatous polyposis coli gene (APC) polymorphisms may influence the risk for colorectal neoplasia. However, results thus far have been inconclusive. We performed a systematic literature search of the Medline, Embase, Cochrane Collaboration, and HuGE databases and reviewed the references of pertinent articles through May 2012. Odds ratios with 95 confidence intervals were used to estimate the association between 3 APC polymorphisms (D1822V, E1317Q, and I1307K) and colorectal neoplasia. In total, 40 studies from 1997 to 2010 were included in this meta-analysis, and individuals with the D1822V variant homozygote VV genotype had a slight decrease in the risk for colorectal neoplasia compared with the wild-type homozygote DD genotype (pooled odds ratio 0.87, 95 confidence interval: 0.77, 0.99). There was a small association between the APC E1317Q polymorphism and a risk for colorectal neoplasia (variant vs. wild-type: pooled odds ratio 1.41, 95 confidence interval: 1.14, 1.76), particularly for colorectal adenomas (variant vs. wild-type: odds ratio 2.89, 95 confidence interval: 1.83, 4.56). Compared with those who carried the wild-type I1307K, Ashkenazi Jews who carried the I1307K variant were at a significantly increased risk for colorectal neoplasia, with a pooled odds ratio of 2.17 (95 confidence interval: 1.64, 2.86). Our study suggests that APC is a candidate gene for colorectal neoplasia susceptibility.