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

## TL;DR

This study found that specific genetic variations in the Foxp3 gene are linked to a lower risk of bladder cancer and may affect patient survival.

## Contribution

The study identifies specific Foxp3 gene SNPs as potential risk factors for bladder cancer and survival outcomes.

## Key findings

- The CA/AA genotype of rs3761548 is associated with a significantly lower risk of bladder cancer.
- The AA genotype of rs3761548 is linked to a markedly lower overall survival rate in bladder cancer patients.
- The rs5902434 polymorphism shows a decreased risk of bladder cancer but no significant effect on survival.

## Abstract

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.

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.

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.

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.