A Functional Polymorphism in the Epidermal Growth Factor Gene Is Associated With Risk for Hepatocellular Carcinoma

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 141; no. 1; pp. 141 - 149
• Main Authors: Abu Dayyeh, Barham K., Yang, May, Fuchs, Bryan C., Karl, Daniel L., Yamada, Suguru, Sninsky, John J., O'Brien, Thomas R., Dienstag, Jules L., Tanabe, Kenneth K., Chung, Raymond T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2011
• Subjects: Adult; Antiviral Agents - therapeutic use; Black or African American - genetics; Cancer; Carcinoma, Hepatocellular - ethnology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Disease Progression; ErbB Receptors - blood; ErbB Receptors - genetics; Female; Gastroenterology and Hepatology; Gene Frequency; Genetic Predisposition to Disease; HCV; 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 Disease; Liver Neoplasms - ethnology; Liver Neoplasms - genetics; Liver Neoplasms - virology; Logistic Models; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Tumor; United States; White People - genetics; United States; Prognosis; HALT-C; EGF; CI; Tumor; HCV; HR; AFP; Liver Disease; EGFR; Cancer; Hepatitis C Antiviral Long-term Treatment against Cirrhosis; epidermal growth factor receptor; hazard ratio; α-fetoprotein; confidence interval; epidermal growth factor
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2011.03.045

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. 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. 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. 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.