Abstract 3613: Toenail selenium is associated with a decreased risk of advanced prostate cancer.
Authors: Geybels Milan S. , Verhage Bas A.J. , van Schooten Frederik J. , Goldbohm Alexandra , van den Brandt Piet A. 
Published: August 2014

Abstract
Introduction: Selenium status has been associated with a reduced risk of total prostate cancer (PCa) and there is evidence that the association is more pronounced for advanced, clinically relevant PCa. This association, however, has been studied over a relatively narrow range of selenium status and data from low-selenium populations are missing. Most prior studies of selenium status and PCa have used plasma/serum selenium, which reflects recent selenium intake, and few studies have used toenail selenium, which reflects longer exposure time windows. Methods: We studied the association of toenail selenium and advanced PCa risk in the Netherlands Cohort study, which includes 58,279 men aged 55 to 69 years. The study has a case-cohort design; a random subcohort was sampled at baseline in 1986 and incident advanced (stage III/IV) PCa cases were identified during 17.3 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Results: The study population included 898 advanced PCa cases and 1,203 subcohort members. The average toenail selenium concentration among subcohort members was 0.549 μg/g (standard deviation: 0.128). Toenail selenium was associated with a reduced risk of advanced PCa and adjusted HRs for increasing quintiles of toenail selenium were 1.00 (reference), 0.69 (95% CI: 0.52, 0.90), 0.45 (95% CI: 0.34, 0.60), 0.32 (95% CI: 0.24, 0.44), and 0.24 (95% CI: 0.17, 0.33) (P for trend &lt;0.01). The association was more pronounced for men diagnosed during later follow-up, and adjusted HRs (0.045 μg/g increment; size central quintile) for men diagnosed during ≤6 years, &gt;6 to 12 years, and &gt;12 years of follow-up were 0.91 (95% CI: 0.85, 0.98), 0.85 (95% CI: 0.75, 0.96), and 0.77 (95% CI: 0.71, 0.84), respectively. Conclusion: Toenail selenium was associated with a substantial decrease in risk of advanced PCa, particularly during later follow-up. If our results can be confirmed, a prevention trial of selenium and PCa in a low-selenium population may be justified. Selenium exerts important biological functions through its presence in selenoproteins and genetic variation in the major selenoproteins glutathione peroxidase 1 (GPX1) and selenoprotein P (SEPP1) has been associated with the risk of PCa. In a next analysis, in the same population, we will study the association of common variation in GPX1 and SEPP1 with advanced PCa risk, and we will evaluate SNP-selenium interactions.
Citation Format: Milan S. Geybels, Bas A.J. Verhage, Frederik J. van Schooten, Alexandra Goldbohm, Piet A. van den Brandt. Toenail selenium is associated with a decreased risk of advanced prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3613. doi:10.1158/1538-7445.AM2013-3613