Özet:

Objective(s): FOXP3 gene is an X-linked gene that encodes FOXP3 protein, an essential transcription factor in CD4+CD25+FOXP3+ regulatory T (Treg) cells.  We aimed, in the present study, to investigate the association of two FOXP3 polymorphisms, -2383 C/T (rs3761549) and IVS9+459 T/C (rs2280883), with lung cancer. Materials and Methods:  In a case-control study we analyzed genotypes and alleles frequencies at -2383 C/T and IVS9+459 T/C positions in 156 patients with lung cancer and 156 age and sex matched healthy controls in Southern Iranian population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The data were verified by direct automated DNA sequencing. Results: The frequency of -2383 T allele was significantly higher in the patients than in the control group (11.8% versus 5.9%, P-value=0.04, OR=2.13, 95%CI=1.04-4.54). T allele frequency at IVS9+459 T/C position was higher, compared to the controls, in the patients who presented the disease over 55 years old (69.9% versus 59.1%, P-value=0.04, OR=1.61, 95%CI=1.01-2.55) and also in SCLC patients (77.8% versus 59.1%, P-value=0.03, OR=2.42, 95%CI=1.05-5.59). No significant differences were found in the genotypes and haplotypes distributions between the cases and controls. A high degree of linkage disequilibrium was observed between two polymorphisms.  Conclusion: As the first study dealing with -2383 C/T and IVS9+459 T/C in lung cancer, our data conclusively suggest the association of -2383 T allele with susceptibility to lung cancer in Iranian population. The association of IVS9+459 T allele with susceptibility to lung cancer in old patients suggests the age-dependent effects of FOXP3 gene on cancer occurrence.

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