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September 24, 2010

Higher serum selenium levels linked with lower prostate cancer risk

Higher serum selenium levels linked with lower prostate cancer risk

An article published online on September 17, 2010 in the journal Cancer Epidemiology, Biomarkers & Prevention reports a benefit between higher levels of the mineral selenium and a reduced risk of prostate cancer. The finding contradicts the conclusion of other research which failed to determine a protective benefit for selenium in the disease.

In their introduction, the authors remark that "Increased intake of selenium has been suggested to have anticarcinogenic effects and numerous mechanisms have been proposed to explain this property: reduction of DNA damage, oxidative stress or inflammation; also, induction of phase II enzymes, enhancement of immune response, inhibition of cell cycle and angiogenesis and induction of apoptosis . . . Intervention studies in humans have shown that supplementation of selenium leads to an increase in concentration and/or activity of circulating selenoproteins, such as selenoprotein P (SePP) or glutathione peroxidases (GPx), and plasma SePP and GPx3 represent common markers of selenium status. Since GPx are important components of the redox control system in humans, reduction of cellular oxidative stress and subsequent DNA damage could be a major mechanism to explain the anticancer effects of selenium."

The current case-control study included participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg study which sought to evaluate the association between lifestyle and metabolic factors, and cancer risk. The European researchers age-matched 248 men diagnosed with prostate cancer with 492 control subjects who did not have the disease. Serum samples obtained upon enrollment were analyzed for selenium, selenoprotein P concentrations, and activity of glutathione peroxidase, a selenium-containing antioxidant that functions in the detoxification of hydrogen peroxide. Genotyping was carried out to determine variations in genes that encode for the latter two factors.

A reduction in prostate cancer risk was found in association with higher serum levels of selenium. When participants were divided into four groups according to selenium status, those whose selenium was in the third highest group had a 39 percent lower risk of prostate cancer than those whose selenium levels were lowest. This reduction in risk lessened among those whose selenium levels were in the top quarter. Serum glutathione peroxidase levels exhibited a similar protective pattern.

When high-grade cancers were separately examined, increased selenium status was associated with an even greater protective effect. Additionally, a variation in the gene that encodes for one type of glutathione peroxidase further amplified selenium's protective benefit.

"Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer aetiology, which warrants confirmation in future studies," the authors conclude.

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Prostate cancer overview

Measures to prevent prostate cancer (PC) must be a routine part of the counsel that general practitioners and internists give their patients. Selenium intake of at least 200 mcg a day should be a consideration in the prevention of PC. Low plasma selenium is associated with a four- to fivefold increased risk of PC. In addition, levels of plasma selenium also decrease with age, resulting in middle-aged to older men being at a higher risk for low selenium levels. Ideally, baseline levels of selenium should be obtained before beginning routine selenium supplementation. It would make sense to begin such a micronutrient and mineral assessment at age 25 and perhaps every 10 years thereafter.

Selenium also has been shown to have a significant antineoplastic effect on breast, lung, liver, and small intestinal tumor cells. Supplementation with selenium enhanced the chemotherapeutic effects of Taxol (paclitaxel) and Adriamycin (doxorubicin) in these cells beyond that seen when the chemotherapeutic drugs were used alone. In studies of the PC cell lines LNCaP and PC-3, the addition of Taxol or Adriamycin, in combination with selenium, caused small but significant inhibition of the PC cell growth. In the cited studies, the optimal inhibition of tumor growth occurred when the plasma selenium level was between 4 -40 ng/mL after 72 hours of treatment.

A large-scale study of almost 11,000 men in Maryland showed that the protective effects of high selenium levels, and similarly that of the alpha-tocopherol isomer of vitamin E, were only observed when the concentrations of the gamma tocopherol isomer of vitamin E were also high. In this study, the risk of PC declined with increasing concentrations of alpha-tocopherol, with the highest concentration associated with a 68% PC risk reduction. For gamma-tocopherol, men with levels in the highest fifth of the distribution had a fivefold greater reduction in the risk of developing PC than men in the lowest fifth (p = .002). The observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium suggested that combined alpha- and gamma-tocopherol supplements, used in conjunction with selenium, should be considered in future PC prevention trials.

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