Hypoxia inducible factor-1alpha gene polymorphism G1790A and its interaction with tobacco and alcohol consumptions increase susceptibility to hepatocellular carcinoma.

Background and Objectives: The aim of this study was to examine the potential associations of two hypoxia inducible factor-1α (HIF-1α) gene polymorphisms, C1772T and G1790A, with the susceptibility and clinicopathological status of hepatocellular carcinoma. Methods: A total of 449 subjects, including 347 healthy controls and 102 patients with hepatocellular carcinoma, were recruited in this study and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses to estimate the impact of these two polymorphic variants on hepatocellular carcinoma. Results: G1790A heterozygotes showed a higher risk for hepatocellular carcinoma, compared with GG genotypes after adjusting for other confounders (AOR = 3.97; 95%CI = 1.70-9.22), indicating a significant association between hepatocellular carcinoma susceptibility and G1790A polymorphism. Moreover, results also revealed the presence of synergistic effect between gene polymorphism of HIF-1α G1790A and environmental risk factors, such as tobacco and alcohol consumptions while there was no significant association between HIF-1α gene polymorphism and clinicopathological parameters of hepatocellular carcinoma. Conclusions: Genetic polymorphism at G1790A of HIF-1α is an important factor for determining the susceptibility to hepatocellular carcinoma. The interaction effects of G1790A heterozygotes to tobacco and to alcohol consumption significantly increase the risk to develop hepatocellular carcinoma.