title: HFE C282Y homozygotes are at increased risk of breast and colorectal cancer.
abstract: The evidence that mutations in the HFE gene for hemochromatosis are associated with increased cancer risk is inconsistent. The Melbourne Collaborative Cohort Study is a prospective cohort study that commenced recruitment in 1990. Participants born in Australia, New Zealand, the United Kingdom, or Ireland (n = 28,509) were genotyped for the HFE C282Y (substitution of tyrosine for cysteine at amino acid 282) variant. Incident cancers were ascertained from Australian cancer registries during an average of 14 years follow-up. Hazard ratios (HRs), confidence intervals (CIs), and P values were obtained from separate Cox regression analyses for colorectal, breast, and prostate cancers, all other solid cancers, and all cancers. Compared to those with no C282Y variant, C282Y homozygotes were at increased risk of colorectal cancer (HR = 2.28; 95% CI = 1.22, 4.25; P = 0.01) and female C282Y homozygotes were at increased risk of developing breast cancer (HR = 2.39; 95% CI = 1.24, 4.61; P = 0.01), but male C282Y homozygotes were not at increased risk for prostate cancer (HR = 0.96; 95% CI = 0.43, 2.15; P = 0.92). C282Y/H63D compound heterozygotes were not at increased risk for colorectal cancer (HR = 1.27; 95% CI = 0.80, 2.01), breast cancer (HR = 1.16; 95% CI = 0.74, 1.84), or prostate cancer (HR = 1.08; 95% CI = 0.68, 1.70).
  
  
  CONCLUSIONS
  HFE C282Y homozygotes have twice the risk of colorectal and breast cancer compared with those individuals without the C282Y variant.
authors.affiliation: Gut and Liver, Murdoch Childrens Research Institute, Melbourne, VIC, Australia. nicholas.osborne@mcri.edu.au
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Osborne
authors.forename: Lyle C
authors.initials: LC
authors.lastname: Gurrin
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Allen
authors.forename: Clare C
authors.initials: CC
authors.lastname: Constantine
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Gertig
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
authors.forename: Lawrie W
authors.initials: LW
authors.lastname: Powell
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D014168:Transferrin / Q000378:metabolism
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D007501:Iron