title: A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma.
abstract: OBJECTIVE
  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: Gastrointestinal Unit, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors: Barham K
authors: BK
authors: Abu Dayyeh
authors: May
authors: M
authors: Yang
authors: Bryan C
authors: BC
authors: Fuchs
authors: Daniel L
authors: DL
authors: Karl
authors: Suguru
authors: S
authors: Yamada
authors: John J
authors: JJ
authors: Sninsky
authors: Thomas R
authors: TR
authors: O'Brien
authors: Jules L
authors: JL
authors: Dienstag
authors: Kenneth K
authors: KK
authors: Tanabe
authors: Raymond T
authors: RT
authors: Chung
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D018450:Disease Progression; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C512478:EGFR protein, human; D066246:ErbB Receptors