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.
RCT Entities:
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.
Authors: L Bolondi; S Sofia; S Siringo; S Gaiani; A Casali; G Zironi; F Piscaglia; L Gramantieri; M Zanetti; M Sherman Journal: Gut Date: 2001-02 Impact factor: 23.059
Authors: Majid Shahbazi; Vera Pravica; Najma Nasreen; Hana Fakhoury; Anthony A Fryer; Richard C Strange; Peter E Hutchinson; Joy E Osborne; John T Lear; Andrew G Smith; Ian V Hutchinson Journal: Lancet Date: 2002-02-02 Impact factor: 79.321
Authors: Rosario F Velázquez; Manuel Rodríguez; Carmen A Navascués; Antonio Linares; Ramón Pérez; Nieves G Sotorríos; Isabel Martínez; Luis Rodrigo Journal: Hepatology Date: 2003-03 Impact factor: 17.425
Authors: H Tsukuma; T Hiyama; S Tanaka; M Nakao; T Yabuuchi; T Kitamura; K Nakanishi; I Fujimoto; A Inoue; H Yamazaki Journal: N Engl J Med Date: 1993-06-24 Impact factor: 91.245
Authors: P Blanc; H Etienne; M Daujat; I Fabre; F Zindy; J Domergue; C Astre; B Saint Aubert; H Michel; P Maurel Journal: Gastroenterology Date: 1992-04 Impact factor: 22.682
Authors: S E Singletary; F L Baker; G Spitzer; S L Tucker; B Tomasovic; W A Brock; J A Ajani; A M Kelly Journal: Cancer Res Date: 1987-01-15 Impact factor: 12.701