Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands)

Background & Aims: Heterozygosity for the Cys282Tyr transition in the HFE-gene is associated with slightly increased iron levels and may therefore be a potential risk factor for colorectal cancer.Methods: We studied the relationship between Cys282Tyr-heterozygosity and colorectal cancer using a case-control design. The 240 colorectal cancer cases and 635 controls in our study were derived from a prospective cohort study of 12,242 postmenopausal women, who were invited for an experimental breast cancer screening program in Utrecht, the Netherlands. The women were age 51-69 at time of inclusion and were followed for a period of 20 years. HFE genotyping was performed by PCR and allele-specific oligonucleotide (ASO) hybridization.Results: The risk of colorectal cancer was higher for women who were heterozygous for the Cys282Tyr mutation, than for those who were Cys282Tyr-wildtypes, although this was not statistically significant (Age-adjusted OR = 1.2, 95% CI: 0.6-2.2). Cys282Tyr-heterozygotes who smoked seemed to be at higher risk of colorectal cancer, although the p-value for interaction was not significant (p-value 0.42).Conclusions: The Cys282Tyr mutation is not associated with an increased risk for colorectal cancer in postmenopausal women, although in combination with smoking a slightly increased risk cannot be excluded.