Nucleotide variation in Foxp3 gene and prognosis of bladder cancer: a case-control study

Foxp3基因核苷酸变异与膀胱癌预后:一项病例对照研究

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Abstract

BACKGROUND: Numerous researches have investigated the correlation between single nucleotide polymorphisms (SNPs) in the transcription factor forkhead box protein 3 (Foxp3) gene and the development of various cancers. However, the relationship of Foxp3 polymorphism and bladder cancer (BC) remain unclear. METHOD: This hospital-based case-control study enrolled a total of 316 patients diagnosed with BC and 643 healthy controls. Two Foxp3 SNPs (rs3761548 C/A, rs5902434 del/ATT) were selected, and genotyping of the samples was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. SPSS and online SNPstats software were used to determine the disparities between groups. RESULTS: For the rs3761548 C/A polymorphism, patients with the CA/AA genotype showed a notable decrease in the case group (22.1% versus 34.8%, P = 0.003, OR = 0.61, 95%CI = 0.44-0.85), and the heterozygous CA genotype presented a distinctly lower risk for BC (P = 0.0003, OR = 0.43, 95%CI = 0.26-0.70). Notably, individuals who were homozygous for the AA genotype demonstrated a markedly lower overall survival (OS) rate compared to those with the CC/CA genotypes (P = 0.03, OR = 5.89, 95%CI = 1.23-28.15), after adjusting for factors such as age, gender, smoking status, tumor grade, metastasis, and clinical stage. For the rs5902434 del/ATT polymorphism, a decreased risk was observed across the codominant and over-dominant models with statistical significance (codominant model: P = 0.01, OR = 0.61, 95%CI = 0.42-0.89; over-dominant model: P = 0.004, OR = 0.60, 95%CI = 0.42-0.85), and no significant association was observed between the rs5902434 polymorphism and patient's OS rate. CONCLUSIONS: Our findings indicate that Foxp3 polymorphisms may be associated with BC susceptibility, and that rs3761548 could potentially serve as an independent risk factor for the OS rate.

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