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

Barham K. Abu Dayyeh, May Yang, Bryan C. Fuchs, Daniel L. Karl, Suguru Yamada, John J. Sninsky, Thomas R. O'Brien, Jules L. Dienstag, Kenneth K. Tanabe, Raymond T. Chung

Research output: Contribution to journalArticle

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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, 1.054.23; 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.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalGastroenterology
Volume141
Issue number1
DOIs
StatePublished - Jul 2011
Externally publishedYes

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Epidermal Growth Factor
Hepatocellular Carcinoma
Genes
Genotype
Fibrosis
Demography
Incidence
Chronic Hepatitis C
Hepatitis C
Serum
Proportional Hazards Models
Antiviral Agents
Single Nucleotide Polymorphism
Case-Control Studies
Alleles
Odds Ratio
Confidence Intervals

Keywords

  • Cancer
  • HCV
  • Liver Disease
  • Prognosis
  • Tumor

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Abu Dayyeh, B. K., Yang, M., Fuchs, B. C., Karl, D. L., Yamada, S., Sninsky, J. J., ... Chung, R. T. (2011). A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma. Gastroenterology, 141(1), 141-149. https://doi.org/10.1053/j.gastro.2011.03.045

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

In: Gastroenterology, Vol. 141, No. 1, 07.2011, p. 141-149.

Research output: Contribution to journalArticle

Abu Dayyeh, BK, Yang, M, Fuchs, BC, Karl, DL, Yamada, S, Sninsky, JJ, O'Brien, TR, Dienstag, JL, Tanabe, KK & Chung, RT 2011, 'A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma', Gastroenterology, vol. 141, no. 1, pp. 141-149. https://doi.org/10.1053/j.gastro.2011.03.045
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. / A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma. In: Gastroenterology. 2011 ; Vol. 141, No. 1. pp. 141-149.
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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, 1.054.23; 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.",
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AU - Abu Dayyeh, Barham K.

AU - Yang, May

AU - Fuchs, Bryan C.

AU - Karl, Daniel L.

AU - Yamada, Suguru

AU - Sninsky, John J.

AU - O'Brien, Thomas R.

AU - Dienstag, Jules L.

AU - Tanabe, Kenneth K.

AU - Chung, Raymond T.

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AB - 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, 1.054.23; 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.

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