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

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

Author information

1
Gastrointestinal Unit, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA.

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.

PMID:
21440548
PMCID:
PMC3129453
DOI:
10.1053/j.gastro.2011.03.045
[Indexed for MEDLINE]
Free PMC Article

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