Toll-like receptor 4 genetic variants and prognosis of breast cancer

Despite the knowledge of many genetic alterations present in breast cancer, the complexity of this disease precludes placing its biology into a simple conceptual framework. 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 breast cancer. Four functional TLR4 polymorphisms (-2242T/C, Asp299Gly, Thr399Ile, and +3725G/C) were genotyped in a total of 665 breast cancer patients and 768 healthy controls. Data were analyzed using the chi-squared test. Results showed that the prevalence of TLR4 +3725GC and CC genotypes were significantly increased in breast cancer cases when compared with controls [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.08-1.73, P = 0.008 and OR = 2.34, 95% CI = 1.66-3.35, P < 0.0001, respectively]. Also, the frequency of TLR4 +3725C allele was significantly higher in breast cancer patients (P < 0.0001). The -2242T/C polymorphism did not show any significant differences between cases and controls. In addition, when analyzing the survival time of breast cancer patients with TLR4 +3725G/C polymorphism, cases with +3725C allele had significantly shorter survival time overall (P = 0.006). These results suggested that polymorphism in TLR4 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.