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; 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.