Functional Foxp3 polymorphisms and the susceptibility to cancer An update meta-analysis

Background: Forkhead box P3 (Foxp3) plays important roles in the development and pathogensis of cancer. To investigate the association of 3 polymorphisms of Foxp3 (rs3761548, rs 3761549 and rs2280883) and cancer risk, an updated meta-analysis was performed. Methods: Around 11 studies including 4344 cancer patients and 4665 healthy controls were selected for this meta-analysis. There were nine studies with 3783 cases and 4096 controls for rs3761548, 4 studies with 1669 cases and 1613 controls for rs3761549 and 4 studies with 1821 cases and 1799 controls for rs2280883. Odds radios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. Results: Meta-analysis showed that rs3761548 was associated with an increased cancer risk in the overall population under the recessive model (AA vs CA+CC: OR=1.45, 95% CI=1.03-2.02, P=.03). No association was found between rs3761549, rs2280883 polymorphisms, and cancer susceptibility in the overall population. Nonetheless, in the genotyping methods subgroup analysis of rs2280883, a lower risk of cancer was found in studies using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) under the allelic model (C vs T: OR=0.70, 95% CI=0.52-0.95, P=.02), heterozygote model (TC vs TT: OR=0.60, 95% CI=0.41-0.87, P=.008) and dominant model (CC+TC vs TT: OR=0.63, 95% CI=0.45-0.90, P=.01). In the subgroup analysis by cancer types showed C allele or TC carriers were insusceptible to cancer under 3 genetic models (C vs T: OR=0.78, 95% CI=0.64-0.95, P=.01; TC vs TT: OR=0.50, 95% CI=0.32-0.79, P=.003; CC+TC vs TT: OR=0.64, 95% CI=0.51-0.82, P<. 001). Conclusion: Our results suggest that rs3761548 polymorphism is associated with cancer risk.