Date presented at the Annual Meeting of the American Association for Cancer Research held this year in Washington, D.C., from April 6 to 10, shows that a greater level of toenail selenium was associated with a significant decrease in the risk for advanced prostate cancer.[1]

Selenium, a trace mineral that is essential to good health and exerts important biological functions. As part of a healthy diet, it is required only in small amounts [2] [3]. Selenium is incorporated into proteins to make selenoproteins, which are important antioxidant enzymes. These selenoproteins help prevent cellular damage from free radicals, which are natural by-products of oxygen metabolism that may contribute to the development of chronic diseases, cardiovascular disease and different forms of cancer [3] [4]. Through its presence in selenoproteins and genetic variation in the major selenoproteins glutathione peroxidase 1 (GPX1)and selenoprotein P (SEPP1)selenium has been associated with the risk of advanced prostate cancer.

Clinically relevant
The data supporting the suggestion that selenium is associated with a reduced risk of advanced prostate cancer may be important for the development of new strategies in fighting the disease. ?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 Studyon 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. In that month, all he cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status.[5] 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.

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Poor prognosis
?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.?

Measuring long-term exposure
Geybels 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% lower risk for advanced prostate cancer compared with men with the lowest toenail selenium levels.

Previous Studies
In a study published in Cancer Epidemiol Biomarkers Prevention (2003) the inverse association between selenium intake and prostate cancer risk was noted.[5] Using data from the same cohort study, researchers evaluated the effects on selenium and noted that the inverse association was more pronounced in ex-smokers than current smokers, and unclear in never-smokers. Their analysis of effect modification by intake of antioxidant vitamins C, E, and the carotenoids alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin showed a strong, significant interaction with beta-cryptoxanthin, and to a lesser extent with vitamin C. These results confirmed their hypothesis that higher selenium intake reduces prostate cancer risk, requiring follow-up studies to find an optimum dose.

Follow-up studies
?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.?

For more information:
[1] Geybels MS, Verhage BAJ, van Schooten FJ, Goldbohm A, van den Brandt PA. Toenail selenium is associated with a decreased risk of advanced prostate cancer. AACR Annual Meeting 2013; Abstract 3613
[2] Thomson CD. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr 2004;58:391-402.
[3] Goldhaber SB. Trace element risk assessment: essentiality vs. toxicity. Regulatory Toxicology and Pharmacology. 2003;38:232-42.
[4] Combs GF, Jr and Gray WP. Chemopreventive agents: Selenium. Pharmacol Ther 1998; 79:179-92.
[5] van den Brandt PA, Zeegers MP, Bode P, Goldbohm RA.
Toenail selenium levels and the subsequentrisk of prostate cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2003 Sep;12(9):866-71.[Abstract][Download Full Document]

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