IFN-γ+874 A/T polymorphism and cancer risk: an updated analysis based on 32 case-control studies

IFN-γ is a T-helper 1 cytokine and plays important roles in modulating almost all the immune responses, such as hematopoiesis, T-cell differentiation, antiproliferative, antiviral, and antitumor activities. A single nucleotide polymorphism (+874A/T) which is located in the first intron of the human IFN-γ gene can putatively influence the secretion of IFN-γ. Results from previous studies on the association of +874A/T polymorphism with different cancer types remained contradictory. In order to derive a more precise estimation of the relationship, a meta-analysis was performed by searching PubMed, Embase, CNKI, and Chinese Biomedicine Database. Thirty two studies including 4524 cases and 5684 controls were collected for IFN-γ+874 A/T polymorphism. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for IFN-γ polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. Overall, no evidence indicated that individuals carrying TT or AT genotypes had significantly increased cancer risk when compared with AA genotype carriers. However, stratified analysis by cancer types indicated a significantly increased risk of breast cancer (TT vs AA: OR=1.58, 95% CI=1.10-2.27, Pheterogeneity=0.26; TT vs

OR=1.53, 95%CI=1.14-2.06, Pheterogeneity=0.19). Moreover, significantly elevated risks were observed in African and European populations when population is concerned. Interestingly, when stratified separately by population-based studies and hospital-based studies, significantly elevated risk was found among population-based studies. This meta-analysis suggests that the IFN-γ+874 T allele is a low-penetrant risk factor for cancer development.