Iron Biomarkers in Plasma, HFE Genotypes, and the Risk for Colorectal Cancer in a Prospective Setting

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BACKGROUND:High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis.OBJECTIVE:The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer.DESIGN:This is a prospective nested case-referent study.SETTINGS:The study was performed within the population-based Northern Sweden Health and Disease Study.PATIENTS:The study included 226 cases of colorectal cancer and 437 matched referents.MAIN OUTCOME MEASURES:Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed.RESULTS:The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38–4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59–7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models.LIMITATIONS:Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers.CONCLUSIONS:High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.

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