Tumor Necrosis Factor-α Genotypes Are Associated with Hepatocellular Carcinoma Risk in Taiwanese Males, Smokers and Alcohol Drinkers

Aim: Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, has high prevalence and mortality rates in Taiwan. Tumor necrosis factor-α (TNFα), an important proinflammatory cytokine, is involved in multiple physiological and pathogenic phenomena that lead to the destruction and dysregulation of tissues. The present study aimed to evaluate the contribution of TNFA genotype, together with cigarette smoking and alcohol drinking lifestyle to the risk of HCC.

Materials and methods: In this hospital-based case-control study, association of TNFA single-nucleotide polymorphisms -1031T/C, -863C/A, -857T/C, -308G/A and +489A/G, with HCC risk were examined in 298 patients with HCC and 889 age- and gender-matched healthy controls.

Results: The percentages of AA, AG and GG TNFA -308G/A were 6.4%, 18.1% and 75.5% in the HCC patient group and 2.0%, 16.0% and 82.0% in the non-cancer control group, respectively. The AA and AG genotypes were associated with 3.42- and 1.23-fold higher odds of HCC than the GG genotype (95% confidence interval=1.76-6.63 and 0.87-1.74, respectively). No such significant difference was found for other polymorphic sites. We further stratified the populations by gender, cigarette smoking and alcohol drinking status to investigate their combined contributions with TNFA -308G/A genotype to HCC risk. The results showed that the AA and AG genotypes of TNFA -308G/A increased HCC susceptibility which was obvious among males, smokers, and alcohol drinkers, but not females, non-smokers, or non-drinkers (p=0.0003, 0.0003, 0.0014, 0.6127, 0.7442 and 0.3010, respectively).

Conclusion: Our results suggest that the AA and AG polymorphism of TNFA -308G/A genotypes associated with HCC risk in Taiwan, particularly among males, smokers and alcohol drinkers.