HFE C282Y homozygotes are at increased risk of breast and colorectal cancer

Authors

  • Nicholas J. Osborne,

    Corresponding author
    1. Gut and Liver, Murdoch Childrens Research Institute, Melbourne, VIC Australia
    2. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
    3. Department of Paediatrics, the University of Melbourne, Melbourne, VIC, Australia
    • Murdoch Childrens Research Institute, The Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia
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    • fax: 613 9090 5251.

  • Lyle C. Gurrin,

    1. Gut and Liver, Murdoch Childrens Research Institute, Melbourne, VIC Australia
    2. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
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  • Katrina J. Allen,

    1. Gut and Liver, Murdoch Childrens Research Institute, Melbourne, VIC Australia
    2. Department of Paediatrics, the University of Melbourne, Melbourne, VIC, Australia
    3. Department of Gastroenterology, The Royal Children's Hospital, Melbourne, VIC, Australia
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  • Clare C. Constantine,

    1. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
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  • Martin B. Delatycki,

    1. Department of Paediatrics, the University of Melbourne, Melbourne, VIC, Australia
    2. Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, VIC, Australia
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  • Christine E. McLaren,

    1. Department of Epidemiology, University of California, Irvine, CA
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  • Dorota M. Gertig,

    1. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
    2. Victorian Cervical Cytology Registry, Melbourne, VIC, Australia
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  • Gregory J. Anderson,

    1. Queensland Institute of Medical Research, Brisbane QLD, Australia
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    • G.A. is Senior Research Fellow

  • Melissa C. Southey,

    1. Department of Pathology, University of Melbourne, Melbourne, VIC, Australia
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  • John K. Olynyk,

    1. Department of Gastroenterology, Fremantle Hospital, Fremantle, WA, Australia
    2. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia
    3. Western Australian Institute of Medical Research, Perth, WA, Australia
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  • Lawrie W. Powell,

    1. Queensland Institute of Medical Research, Brisbane QLD, Australia
    2. University of Queensland, Brisbane, QLD, Australia
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  • John L. Hopper,

    1. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
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  • Graham G. Giles,

    1. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
    2. Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, VIC Australia
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  • Dallas R. English

    1. Centre for MEGA Epidemiology, the University of Melbourne, Melbourne, VIC, Australia
    2. Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, VIC Australia
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  • Potential conflict of interest: Nothing to report.

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). Conclusion: HFE C282Y homozygotes have twice the risk of colorectal and breast cancer compared with those individuals without the C282Y variant. (HEPATOLOGY 2010.)

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