Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related deaths.[1,2] Cirrhosis is the strongest known risk factor for hepatocellular carcinoma (HCC), cirrhosis related to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections.[3,4] Because current therapies for HCC are limited, and because most diagnoses of HCC are made late in the natural history of the disease, early identification of persons at high risk for HCC is of vital importance in order for targeted screening and chemoprevention to be effective
Higher serum levels of Epidermal Growth Factor (EGF) were observed among subjects with at least one G allele (P=0.08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC
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
Summary
Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related deaths.[1,2] Cirrhosis is the strongest known risk factor for HCC, cirrhosis related to hepatitis C virus (HCV) and hepatitis B virus (HBV) infections.[3,4] Because current therapies for HCC are limited, and because most diagnoses of HCC are made late in the natural history of the disease, early identification of persons at high risk for HCC is of vital importance in order for targeted screening and chemoprevention to be effective. The current screening strategies for HCC are focused on patients with cirrhosis of any cause and patients with long-standing chronic hepatitis B, even in the absence of cirrhosis. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
