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

J Surg Oncol. 2010 Aug 1;102(2):163-9. doi: 10.1002/jso.21539.

Abstract

Background and objectives: The aim of this study was to examine the potential associations of two hypoxia inducible factor-1alpha (HIF-1alpha) 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-1alpha G1790A and environmental risk factors, such as tobacco and alcohol consumptions while there was no significant association between HIF-1alpha gene polymorphism and clinicopathological parameters of hepatocellular carcinoma.

Conclusions: Genetic polymorphism at G1790A of HIF-1alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / epidemiology*
  • Carcinoma, Hepatocellular / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length*
  • Smoking / epidemiology*
  • Taiwan / epidemiology

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit