PPARgamma polymorphisms and cancer risk: a meta-analysis involving 32,138 subjects.

The peroxisome proliferator-activated receptor gamma (PPARgamma) has been suggested to act as a tumor suppressor gene. Two common variations of PPARgamma, P12A (Pro12Ala, rs1801282) and C161T (His447His, rs3856806), are thought to have an effect on susceptibility to various carcinomas but the results are inconsistent. In this meta-analysis, we assessed published studies of the association between two common PPARgamma polymorphisms and cancer risk from 26 studies with 27,677 subjects for PPARgamma P12A, from 4 studies with 4,461 subjects for C161T. No significant associations were found in carriers of the rare Ala allele of the P12A polymorphism versus the common Pro/Pro genotype among the studies. In the subgroup analyses by cancer types, carriers of the Ala variant of P12A polymorphism were associated with protection from colorectal cancer (OR=0.84, 95% CI=0.72-0.98, Pheterogeneity = 0.014), but the inverse association was found in gastric cancer (OR=2.31, 95% CI=1.59-3.36, Pheterogeneity = 0.941). In the stratified analysis by ethnicity, no significant risks were found among Asians, Americans and Caucasians. For PPARgamma C161T, no significant associations were found in any of the studies (OR=1.08, 95% CI=0.95-1.23, Pheterogeneity = 0.430) or subgroups. This meta-analysis suggests that the Ala allele of the PPARgamma P12A polymorphism might be a protective factor for colorectal cancer, but a risk factor for gastric cancer. The PPARgamma C161T is marginally associated with cancer susceptibility.