A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma

Gastroenterology. 2011 Jul;141(1):141-9. doi: 10.1053/j.gastro.2011.03.045. Epub 2011 Mar 24.

Abstract

Background & aims: A single nucleotide polymorphism 61*G (rs4444903) in the epidermal growth factor (EGF) gene has been associated, in 2 case-control studies, with hepatocellular carcinoma (HCC). We tested associations between demographic, clinical, and genetic data and development of HCC, and developed a simple predictive model in a cohort of patients with chronic hepatitis C and advanced fibrosis.

Methods: Black and white subjects from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial (n=816) were followed up prospectively for development of a definite or presumed case of HCC for a median time period of 6.1 years. We used the Cox proportional hazards regression model to determine the hazard ratio for risk of HCC and to develop prediction models.

Results: Subjects with EGF genotype G/G had a higher adjusted risk for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence interval, 1.05-4.23; P=.03). After adjusting for EGF genotype, blacks had no increased risk of HCC risk compared with whites. Higher serum levels of EGF were observed among subjects with at least one G allele (P=.08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC. We developed a simple prediction model that included the EGF genotype to identify patients at low, intermediate, and high risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%, and 26%, respectively.

Conclusions: We associated the EGF genotype G/G with increased risk for HCC; differences in its frequency among black and white subjects might account for differences in HCC incidence between these groups. We developed a model that incorporates EGF genotype and demographic and clinical variables to identify patients at low, intermediate, and high risk for HCC.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans / genetics
  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / ethnology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Disease Progression
  • ErbB Receptors / blood
  • ErbB Receptors / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / ethnology
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • United States

Substances

  • Antiviral Agents
  • EGFR protein, human
  • ErbB Receptors

Grant support