Background: The underlying genetic factors for the development and progression of hepatocellular carcinoma (HCC) are largely unknown. TNFalpha is a well characterized inflammatory mediator and is implicated in the development of HCC. We investigated TNFalpha polymorphisms for association with HCC.
Methods: The study population consisted of 227 HCC patients and 365 age and sex matched Korean controls. TNFalpha polymorphisms (G-238A, C-857T, and C-863A) were genotyped using pyrosequencing analysis. TNFalpha 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 TNFalpha 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. TNFalpha -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]. TNFalpha -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 TNFalpha level was significantly increased in HCC patients with CT+TT genotype for TNFalpha -857 (P=0.018).
Conclusion: Our data imply that TNFalpha G-238A and C-857T, not C-863A, polymorphisms may confer different susceptibilities to the development of HCC with TNFalpha -238A and -857T alleles playing as risk factors.