Toll-like receptor 4 gene polymorphisms and susceptibility to bladder cancer.

Bladder cancer is one of the most common malignancies in the world. Toll-like receptor 4 (TLR4) plays important roles in regulating innate immunity and may affect the development of cancers. Polymorphisms in TLR4 gene have been shown to be associated with impaired immune responses. Here, we investigated the association of TLR4 polymorphisms with bladder cancer. Four TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Il3, and +3725G/C) were genotyped in a total number of 436 bladder cancer patients and 522 healthy controls. Data were analyzed using the Chi-square test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in bladder cancer cases than in controls (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.19-2.10, p = 0.0015, and OR = 2.33, 95%CI = 1.52-3.58, p < 0.0001, respectively). Also, the frequency of TLR4 +3725C allele was significantly higher in bladder cancer patients (p < 0.0001). The -2242T/C, Asp299Gly and Thr399Il3 polymorphisms did not reveal any significant differences between cases and controls. Stratification analysis of the clinical features in the patients demonstrated that cases with invasive cancer were correlated with higher numbers of +3725GC and CC genotype (p = 0.0004 and p = 0.0231). In conclusion, these results indicate that TLR4 +3725G/C polymorphism may be a novel risk factor for bladder cancer in the Chinese population.