title: Cancer risk in HFE C282Y homozygotes: results from the HUNT 2 study.
abstract: OBJECTIVE
  In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes.
  
  
  METHODS
  We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995-1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking.
  
  
  RESULTS
  Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60-2.03] in women and 0.94 [95% CI 0.53-1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17-7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68-1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35-3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence.
  
  
  CONCLUSIONS
  C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.
authors.affiliation: Department of Clinical Chemistry, Trondheim University Hospital, Trondheim, Norway. arne.aasberg@stolav.no
authors.forename: Arne
authors.initials: A
authors.lastname: Asberg
authors.forename: Ketil
authors.initials: K
authors.lastname: Thorstensen
authors.forename: Wenche Ø
authors.initials: WØ
authors.lastname: Irgens
authors.forename: Pål R
authors.initials: PR
authors.lastname: Romundstad
authors.forename: Kristian
authors.initials: K
authors.lastname: Hveem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009664:Norway / Q000453:epidemiology; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins