Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis

Authors

  • C. Ellervik,

    1. From the Department of Clinical Biochemistry, Herlev Hospital, Herlev
    2. Department of Clinical Biochemistry, Naestved Hospital, Naestved
    3. Copenhagen University Hospitals and Faculty of Health Sciences, Copenhagen
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  • A. Tybjærg-Hansen,

    1. Copenhagen University Hospitals and Faculty of Health Sciences, Copenhagen
    2. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen
    3. The Copenhagen City Heart Study, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
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  • B. G. Nordestgaard

    1. From the Department of Clinical Biochemistry, Herlev Hospital, Herlev
    2. Copenhagen University Hospitals and Faculty of Health Sciences, Copenhagen
    3. The Copenhagen City Heart Study, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
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Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
(fax: +45-4488-3311; e-mail: brno@heh.regionh.dk).

Abstract

Abstract.  Ellervik C, Tybjærg-Hansen A, Nordestgaard BG (Herlev Hospital, Herlev; Naestved Hospital, Naestved; Copenhagen University Hospitals and Faculty of Health Sciences, Copenhagen; Rigshospitalet, Copenhagen; The Copenhagen City Heart Study, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark). Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis. J Intern Med 2012; 271: 51–63.

Objective.  Increased iron overload, whether or not owing to the presence of the haemochromatosis genotype C282Y/C282Y, may be associated with an increased risk of cancer. The aim of this study was to test the hypothesis that elevated transferrin saturation levels (as a proxy for iron overload) and haemochromatosis genotype C282Y/C282Y are associated with an increased risk of cancer.

Methods.  We conducted a population-based study of 8763 individuals, of whom 1417 developed a first cancer during 15 years of follow-up, and a meta-analysis. We stratified absolute 10-year risk of cancer by smoking status, an important risk factor.

Results.  In women, transferrin saturation above 60% versus below 50% was associated with a hazard ratio of 3.6 (95% confidence interval (CI): 2.0–6.5; < 0.001) for any cancer; risk of liver cancer was increased in both women and men. In women, the corresponding absolute 10-year risk of any cancer was 34% and 30% in smokers and nonsmokers, respectively. In men, haemochromatosis genotype C282Y/C282Y versus wild type/wild type was associated with a hazard ratio of 3.7 (95% CI: 1.2–12; = 0.01) for any cancer, with a similar trend in women. In men, the corresponding absolute 10-year risk of cancer was 39% and 27% in smokers and nonsmokers, respectively. Other haemochromatosis genotypes were not associated with increased risk of cancer in women or men. From the meta-analysis, the odds ratio of any cancer for transferrin saturation ≥60% versus a reference group was 1.5 (95% CI: 1.2–1.8) for women and men combined.

Conclusions.  We have demonstrated that elevated transferrin saturation levels in women and haemochromatosis genotype C282Y/C282Y in men are associated with increased risk of cancer. Thus, our results support the implementation of cancer screening programmes in patients with iron overload or with C282Y/C282Y.

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