TNFα promoter polymorphism is a risk factor for susceptibility in hepatocellular carcinoma in Korean population

Abstract

Background

The underlying genetic factors for the development and progression of hepatocellular carcinoma (HCC) are largely unknown. TNFα is a well characterized inflammatory mediator and is implicated in the development of HCC. We investigated TNFα polymorphisms for association with HCC.

Methods

The study population consisted of 227 HCC patients and 365 age and sex matched Korean controls. TNFα polymorphisms (G-238A, C-857T, and C-863A) were genotyped using pyrosequencing analysis. TNFα levels in patients with HCC were determined by enzyme linked immunosorbent assay (ELISA). Logistic regression analysis was used to determine the association with HCC and haplotype was calculated using EH program.

Results

Of three TNFα polymorphisms investigated in our study, C-863A did not correlate with HCC. However, both G-238A and C-857T were found to be significantly associated with HCC. TNFα −238A allele was more frequent in HCC patients than in control [P = 0.012; odds ratio (OR), 1.89; 95% confidence interval (CI), 1.14–3.13]. TNFα −857T was significantly associated with HCC patients (P = 0.001; OR, 1.63; 95% CI, 1.21–2.19). Haplotype analysis revealed that the GTC haplotype (G-238A, C-857T, C-863A) was a risk marker for HCC (P = 0.0021). Serum TNFα level was significantly increased in HCC patients with CT + TT genotype for TNFα −857 (P = 0.018).

Conclusion

Our data imply that TNFα G-238A and C-857T, not C-863A, polymorphisms may confer different susceptibilities to the development of HCC with TNFα −238A and −857T alleles playing as risk factors.

Keywords Hepatocellular carcinoma; Tumor necrosis factor; Polymorphism