title: Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer.
abstract: BACKGROUND
  Iron is a pro-oxidant that may promote carcinogenesis. Mutations in the hemochromatosis (HFE) gene are associated with increased total body iron stores in some individuals. We assessed the risk of colon cancer among individuals with and without HFE gene mutations.
  
  
  METHODS
  We performed a population-based, case-control study in North Carolina. Case patients with colon cancer and control subjects provided information on multiple environmental exposures, including total iron intake and nonsteroidal anti-inflammatory drug (NSAID) use. They also provided a venous blood sample, from which DNA was extracted, amplified, and subjected to diagnostic restriction enzyme mapping to detect two major HFE gene mutations, C282Y and H63D. Data were analyzed with Fisher's exact test and logistic regression. All statistical tests were two-sided.
  
  
  RESULTS
  Thirteen hundred and eight subjects participated (475 case patients, 833 control subjects). The allele frequencies of the H63D and C282Y mutations were greater among case patients (0.11 and 0.046, respectively) than among control subjects (0.09 and 0.044, respectively; P =.14 and P =.85, respectively). When we controlled for age, race, sex, red meat consumption, NSAID use, and total iron intake, subjects with any HFE gene mutation were more likely to have colon cancer than subjects with no HFE gene mutations (adjusted odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.07 to 1.87). The magnitude of the effect was similar for both the H63D (adjusted OR = 1.44, 95% CI = 1.04 to 1.98) and C282Y mutations (adjusted OR = 1.39, 95% CI = 0.88 to 2.19). The risk of colon cancer associated with an HFE gene mutation was similar for those who did and did not have a family history of colon cancer. Among those with HFE mutations, cancer risk increased with increasing age and total iron intake.
  
  
  CONCLUSIONS
  HFE gene mutations are associated with an increased risk of colon cancer. Cancer risk is greatest in mutation carriers who are older or consume high quantities of iron.
authors.affiliation: Center for Gastrointestinal Biology and Disease and Division of Digestive Diseases and Nutrition, University of North Carolina, Chapel Hill 27599-7080, USA. nshaheen@med.unc.edu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Silverman
authors.forename: Temitope
authors.initials: T
authors.lastname: Keku
authors.forename: Laura B
authors.initials: LB
authors.lastname: Lawrence
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Rohlfs
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Martin
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
mesh_terms: D000367:Age Factors; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D005247:Feeding Behavior; D005260:Female; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D006639:Histidine / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D058085:Iron Compounds / Q000008:administration & dosage; D008297:Male; D008460:Meat; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009657:North Carolina; D018570:Risk Assessment; D012307:Risk Factors; D014443:Tyrosine / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D058085:Iron Compounds; D008565:Membrane Proteins; D001224:Aspartic Acid; D014443:Tyrosine; D006639:Histidine; D003545:Cysteine