@article{081c62aeb3784a0396903e3675e2cdf1,
title = "A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma",
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.",
keywords = "Cancer, HCV, Liver Disease, Prognosis, Tumor",
author = "{Abu Dayyeh}, {Barham K.} and May Yang and Fuchs, {Bryan C.} and Karl, {Daniel L.} and Suguru Yamada and Sninsky, {John J.} and O'Brien, {Thomas R.} and Dienstag, {Jules L.} and Tanabe, {Kenneth K.} and Chung, {Raymond T.}",
note = "Funding Information: The authors appreciate the efforts of Joe Catanese and the Celera High Throughput group for generating genotyping data, of Dr David Ross and the Computational Biology group for bioinformatics support, and of Charles Rowland and Robert Lagier for preliminary statistical analysis. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA: (contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, and Donna Giansiracusa, RN; University of Connecticut Health Center , Farmington, CT: (grant M01RR-06192 ) Herbert L. Bonkovsky, MD, Gloria Borders, RN, and Michelle Kelley, RN, ANP; Saint Louis University School of Medicine, St Louis, MO: (contract N01-DK-9-2324) Adrian M. Di Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth M. Brunt, MD, and Debra King, RN; Massachusetts General Hospital , Boston, MA: (contract N01-DK-9-2319, grant M01RR-01066 ; and grant 1 UL1 RR025758-01 , Harvard Clinical and Translational Science Center ) Andrea E. Reid, MD, Atul K. Bhan, MD, Wallis A. Molchen, and David P. Lundmark; University of Colorado Denver, School of Medicine , Aurora, CO: (contract N01-DK-9-2327, grant M01RR-00051 , and grant 1 UL1 RR 025780-01 ) Gregory T. Everson, MD, Thomas Trouillot, MD, Marcelo Kugelmas, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, and Carol McKinley, RN; University of California–Irvine , Irvine, CA: (contract N01-DK-9-2320 and grant M01RR-00827 ) Timothy R. Morgan, MD, John C. Hoefs, MD, John R. Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, and Choon Park, RN; University of Texas Southwestern Medical Center , Dallas, TX: (contract N01-DK-9-2321, grant M01RR-00633 , and grant 1 UL1 RR024982-01 , North and Central Texas Clinical and Translational Science Initiative ) William M. Lee, MD, Thomas E. Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN, Rivka Elbein, RN, BSN, and Nancy Liston, MPH; University of Southern California , Los Angeles, CA: (contract N01-DK-9-2325 and grant M01RR-00043 ) Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones, RN, and Susan L. Milstein, RN; University of Michigan Medical Center , Ann Arbor, MI: (contract N01-DK-9-2323, grant M01RR-00042 , and grant 1 UL1 RR024986 , Michigan Center for Clinical and Health Research ) Anna S. Lok, MD, Robert J. Fontana, MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, and R. Tess Bonham, BS; Virginia Commonwealth University Health System , Richmond, VA: (contract N01-DK-9-2322 and grant M01RR-00065 ) Mitchell L. Shiffman, MD, Richard K. Sterling, MD, MSc, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, and Paula Smith, RN; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD: Marc G. Ghany, MD, T. Jake Liang, MD, David Kleiner, MD, PhD, Yoon Park, RN, Elenita Rivera, RN, and Vanessa Haynes-Williams, RN; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: James E. Everhart, MD, MPH, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H. Hoofnagle, MD, and Elizabeth C. Wright, PhD; University of Washington, Seattle, WA: (contract N01-DK-9-2318) Chihiro Morishima, MD, David R. Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, and Natalia Antonov, MEd; New England Research Institutes, Watertown, MA: (contract N01-DK-9-2328) Kristin K. Snow, MSc, ScD, Anne M. Stoddard, ScD, and Teresa M. Curto, MSW, MPH; Inova Fairfax Hospital, Falls Church, VA: Zachary D. Goodman, MD, PhD; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, and Robert P. Perrillo, MD. ",
year = "2011",
month = jul,
doi = "10.1053/j.gastro.2011.03.045",
language = "English (US)",
volume = "141",
pages = "141--149",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",
}