Toenail selenium status and risk of subtypes of head-neck cancer: The Netherlands Cohort Study

Background: There is limited prospective data on the relationship between selenium status and the risk of head-neck cancer (HNC) and HNC subtypes (i.e., oral cavity cancer [OCC], oro-/hypopharyngeal cancer [OHPC] and laryngeal cancer [LC]). Therefore, we investigated the association between toenail selenium, reflecting long-term selenium exposure, and HNC risk within the Netherlands Cohort Study. Methods: At baseline, 120,852 participants completed a self-administered questionnaire about diet and other cancer risk factors and were asked to provide toenail clippings. After 20.3 years of follow-up, 294 cases of HNC (95 OCC, 62 OHPC, two oral cavity/pharynx unspecified or overlapping and 135 LC) and 2,164 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Results: Toenail selenium status was statistically significantly associated with a decreased risk of HNC overall (multivariate RR for quartile four versus one: 0.55, 95% confidence interval [CI] 0.37-0.82, P trend = 0.001). The association between toenail selenium and risk of HNC overall was stronger among men than women, but no statistically significant interaction with sex was found. Toenail selenium level was also associated with a decreased risk of all HNC subtypes, with statistically significant associations in OHPC and LC. No statistically significant interaction was found between toenail selenium level and cigarette smoking or alcohol consumption for HNC overall. Conclusions: In this large cohort study, we found an inverse association between toenail selenium level and HNC risk. Among HNC subtypes, this association was strongest for OHPC and LC. Furthermore, the association of toenail selenium status with HNC risk was stronger among men than women.