CD4(+)CD25(+) regulatory T cell-mediated immunosuppression is one of the crucial mechanisms that tumor cells use to evade the immune system. The forkhead box P3 (FoxP3) gene regulates regulatory T-cell development and function and may modulate the susceptibility to non-small cell lung cancer (NSCLC). Because a single nucleotide polymorphism (SNP) within the FoxP3 gene (rs3761548 in the promoter region) is associated with susceptibility to Graves' disease, this study detected rs3761548 in a hospital-based case-control study. A total of 192 NSCLC patients and 259 healthy subjects were recruited for the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of FoxP3 SNP. The data showed that the A allele of rs3761548 significantly increased NSCLC risk (P=0.000, OR=2.32, 95%CI=1.736-3.102). The AC genotype, AA genotype, and the combined A variant genotype (AA+AC) were also associated with a higher risk of NSCLC (OR [95%CI]=2.147[1.419-3.247], 4.413[2.359-8.255], and 2.563[1.746-3.761], respectively). Moreover, a significantly higher frequency of AA+AC genotype was observed in patients with stage II NSCLC (OR, 2.053; 95%CI, 1.033-4.078). In conclusion, the data from the current study demonstrated for the first time the association of the FoxP3 SNP with a risk of developing NSCLC in the Chinese Han population.
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