Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate whether TLR3 polymorphisms were associated with susceptibility to HCC. Two polymorphisms in the TLR3 gene, -976T/A and +1234C/T, were tested by polymerase chain reaction-restriction fragment length polymorphism in 466 HCC patients and 482 healthy controls. Results showed that the prevalence of +1234CT genotype and +1234TT genotype were significantly increased in the HCC cases than in controls (odds ratio [OR] =1.51; 95 % confidence interval [CI]; 1.22-1.93; p=0.004 and OR=3.19; 95 % CI, 1.82-5.39; p=1.99 × 10(-5), respectively). The -976T/A polymorphism did not reveal any differences between cases and controls. When analyzing the TLR3 +1234C/T polymorphism with different clinical parameters in HCC patients, the cases who were hepatitis B virus (HBV) carriers had higher number of +1234CT genotype and +1234T allele than those without HBV infection (p=0.032 and p=0.043). These data indicate that TLR3 +1234C/T polymorphism could be a novel risk factor for HCC, especially the HBV-related HCC.