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J Intern Med. 2012 Jan;271(1):51-63. doi: 10.1111/j.1365-2796.2011.02404.x. Epub 2011 Jun 16.

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

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1
Department of Clinical Biochemistry, Herlev Hospital, Herlev Department of Clinical Biochemistry, Naestved Hospital, Naestved Copenhagen, Denmark.

Abstract

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 15years 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; P<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; P=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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