Cohort Study Indicates That Selenium May Be Protective Against Advanced Prostate Cancer


Newswise — WASHINGTON, D.C. — A greater level of toenail selenium was associated with a significant decrease in the risk for advanced prostate cancer, according to data presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

“This could mean, based on our data and based on data from other studies, that selenium is a modifiable risk factor of advanced, clinically relevant prostate cancer,” said Milan S. Geybels, M.Sc., a doctoral candidate in cancer epidemiology at Maastricht University, in Maastricht, the Netherlands.

The Netherlands Cohort Study on diet and cancer is a prospective cohort study that includes 58,279 men who were aged 55 to 69 years at entry in September 1986. Geybels and colleagues analyzed data from 898 men who were diagnosed with advanced prostate cancer during 17.3 years of follow-up of the cohort.

According to Geybels, previous studies investigating the association between selenium levels and prostate cancer have yielded varying results. One large clinical trial showed that selenium supplementation had no protective effect, while several prospective, observational studies indicated that higher levels of selenium were associated with a reduced prostate cancer risk, especially for advanced prostate cancer.

“Our study is interesting because we specifically investigated men with advanced prostate cancer, a type of prostate cancer associated with a poorer prognosis,” Geybels said. “Also, while most of the prior research, including the large clinical trial, involved men with moderate-to-high selenium levels, men in The Netherlands Cohort Study have selenium levels that range from low to moderate. This is important because low selenium is expected to be related to a higher disease risk.”

He and his colleagues chose toenail selenium as the study biomarker because it reflects long-term exposure, as opposed to blood, which is best for monitoring recent selenium exposures.

The data revealed that greater levels of toenail selenium were associated with a substantially reduced risk for advanced prostate cancer. Men with the highest toenail selenium levels had a more than 60 percent lower risk for advanced prostate cancer compared with men with the lowest toenail selenium levels.

“Our findings need to be replicated in further prospective studies, with an extended follow-up for the assessment of incident advanced prostate cancer, and with a wide range of toenail selenium that includes low selenium levels,” Geybels said. “If our results can be confirmed, a prevention trial of selenium and prostate cancer in a low-selenium population may be justified.”

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Abstract Number: 3613

Presenter: Milan S. Geybels, M.Sc.

Title: Toenail selenium is associated with a decreased risk of advanced prostate cancer

Authors: Milan S. Geybels1, Bas A.J. Verhage1, Frederik J. van Schooten1, Alexandra Goldbohm2, Piet A. van den Brandt1. 1Maastricht University, Maastricht, Netherlands; 2TNO, Netherlands

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 <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, >6 to 12 years, and >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.

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