Association of lymphotoxin-α +252A/G, tumor growth factor-β −509C/T and tumor necrosis factor-α -308A/G polymorphisms with hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) risk factors could either be host-genetic or environmental relation. This study aimed to assess the correlation of the three biallelic polymorphisms of lymphotoxin-alpha (LT-α) +252A/G, tumor growth factor-beta 1 (TGF-β1) −509C/T and tumor necrosis factor-alpha (TNF-α) -308A/G with HCC development regardless chronic hepatitis C (CHC) infection. Methods: These polymorphisms were studied among 220 consecutive participants. They were patients with/without HCV-related HCC, and with HCC related to etiologies other than HCV, in addition to the controls. Results: No significant difference between CHC patients and healthy controls regarding the distribution of genotypes of LTα +252A/G, TGF-β1 −509C/T and TNF-α -308A/G was observed. Regardless CHC infection, LTα GG genotype [29.2%, OR =1.99, 95% CI (0.98-4.07), P=0.039], TGF-β CT/TT genotypes [38.3%, OR =2.08, 95% CI (1.0-4.3), P=0.029], and TNF-α AG genotype [(35%, OR=1.27, 95% CI (1.05-1.54), P=0.028)] were more frequent in HCC compared to Non-HCC patients. Moreover, these genotypes were significantly associated (P<0.05) with HCC severity including tumor late stages, high grades, large tumor size, lymph node invasion and distant metastasis. Conclusion: our results demonstrating that LT-α +252A/G, TGF-β1 −509C/T and TNF-α -308A/G might be risk factors for HCC incidence. LT-α GG genotype, TGF-β CT/TT genotypes and TNF-α AG genotype might be correlated with HCC severity and progression.