Polymorphisms in the potential functional regions of the TGF‐β 1 and TGF‐β receptor genes and disease susceptibility in HBV‐related hepatocellular carcinoma patients

Hepatocellular carcinoma (HCC) is a disease of multiple etiologies caused by the accumulation of genetic and epigenetic defects. Current evidence indicates that the transforming growth factor beta (TGF-β) signaling pathway has a significant impact on different cellular process. Members of the TGF-β superfamily (TGF-β1, the type I TGF-β receptor [TβRI], type II TGF-β receptor [TβRII], and type III TGF-β receptor]) play an important role in tumorigenesis. Numerous studies show that genetic polymorphisms in TGF-β superfamily genes are associated with HCC in East Asian populations. We studied 16 single nucleotide polymorphisms (SNPs) in four genes (TGF-β1, TβRI, TβRII, and TβRIII) to examine their associations with hepatocarcinogenesis. A total of 1228 Chinese Han participants were enrolled in the study (881 control participants who were negative for all hepatitis B virus [HBV] serum markers and 347 case participants with HBV-related HCC). Genotyping was conducted using the TaqMan method. The results showed that the frequency of the rs1805110 T allele was significantly higher in the case group than in the control group (P = 0.034). After stratification, the results for rs1805110 remained significant in male participants (P = 0.005), but there was no statistical difference in females. In males, the frequency of the C-C-G-C-A haplotype resulting from SNPs rs1805110, rs2810904, rs1805112, rs284878, and rs1804506 in TβRIII was significantly lower in the case group than in the control group (P = 0.001), whereas the reverse was true for the T-C-G-C-A haplotype (P = 0.036). We conclude that the rs1805110T allele is associated with susceptibility to HBV-related HCC in males. © 2012 Wiley Periodicals, Inc.