What is the role of selenium in prostate cancer risk-reduction?

Answer

Selenium is an essential, nonmetallic trace element that is widely distributed throughout the body. It is a component of multiple antioxidant enzymes and participates in various functions. Epidemiologic studies indicate that selenium is a potential prostate cancer preventive and decreases the growth rate of prostate cancer cells. Plasma, serum, and tissue levels of selenium are inversely associated with the risk of developing prostate cancer.

Selenium is found in Brazil nuts, walnuts, fish (including canned tuna and shellfish), beef, turkey, chicken, eggs, whole grains, garlic, onions, broccoli, cabbage, and mushrooms. One of the problems in obtaining adequate dietary selenium is that the level of selenium in a given plant depends on the soil in which it is growing. For example, produce from the Imperial Valley in California has a higher selenium content than plants grown elsewhere.

Selenium has several forms, each of which may produce differing biologic effects. The protective activities of selenium compounds are thought to be mediated through a metabolite of selenium called methylselenol. Selenomethionine modulates transcript levels of genes involved in cell-cycle and apoptosis pathways, androgen signaling, signal transduction, and transcriptional regulation. At high concentrations, selenomethionine decreases expression of prostate-specific antigen (PSA). Studies with methylselenic acid have shown that similar biologic pathways are affected, but gene expression has distinct differences.

Animal experiments and epidemiologic evidence suggest that selenium has an anticarcinogenic effect due to its action on apoptotic pathways, inhibition of cell proliferation, and antiangiogenesis. Several studies have reported that high selenium levels confer a 50-65% reduction in the risk of prostate cancer over low selenium levels. The Nutrition Prevention of Cancer (NPC) trial reported that the incidence of prostate cancer in men who received selenium supplements was 50% less than in men who received placebo.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) studied the effects of selenium (in the form of selenomethionine, 200 μg daily) and vitamin E alone and in combination in over 35,000 men, but the study was terminated after an average of 5.5 years (SELECT was planned to include 7-12 years of follow-up) when initial results indicated no significant difference between the supplementation and placebo arms. There was a statistically insignificant trend toward more prostate cancer cases in men taking only vitamin E and more cases of diabetes in men taking only selenium.^[57]

In their examination of the disparity between the results of the NPC trial and SELECT, the SELECT investigators noted that the NPC trial participants had deficient levels of selenium, and those with the lowest baseline selenium levels derived the most preventive effect, whereas SELECT participants generally were replete in selenium at baseline.

Additionally, clinical trials of individual selenium supplements in patients at high risk for prostate cancer or with localized prostate cancer have demonstrated no impact on disease progression, and even the possibility of increased risk for disease progression and mortality with high-dose supplementation.^{[58, 59, 60, 61, 62]}This is another reason no individual high-dose antioxidant supplement can currently be promoted for reducing prostate cancer risk.

Of further interest is that in the SELECT trial, selenium supplementation did not reduce prostate cancer risk in men with baseline low selenium status but selenium supplementation in men already replete with selenium from dietary sources increased their risk for aggressive prostate cancer.^[63]Again, these findings support the value of emphasizing dietary sources of selenium over individual supplement use for prostate cancer prevention.

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Mark A Moyad, MD, MPH Research Associate, Phil F Director of Complementary and Alternative Medicine, Department of Urology, University of Michigan Medical Center

Disclosure: Received honoraria from Abbott Labs for speaking and teaching; Received consulting fee from Farr Labs for consulting; Received consulting fee from Guthy Renker for consulting; Received royalty from Guthy Renker for other.

Coauthor(s)

Stanley A Brosman, MD Clinical Professor, Department of Urology, University of California, Los Angeles, David Geffen School of Medicine

Stanley A Brosman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Urological Association, Society for Basic Urologic Research, Society of Surgical Oncology, Society of Urologic Oncology, Western Section of the American Urological Association, Association of Clinical Research Professionals, American Society of Clinical Oncology, International Society of Urology, International Society of Urological Pathology

Disclosure: Nothing to disclose.

Chief Editor

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Sexual Medicine Society of North America, Tennessee Medical Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Endo, Avadel.

Acknowledgements

Gamal Mostafa Ghoniem, MD, FACS Professor of Urology, Chief, Division of Female Urology, Pelvic Reconstructive Surgery, and Voiding Dysfunction, Department of Urology, University of California, Irvine, School of Medicine

Gamal Mostafa Ghoniem, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urogynecologic Society, American Urological Association, International Continence Society, International Urogynaecology Association, and Society of Urodynamics and Female Urology

Disclosure: Astellas Honoraria Speaking and teaching; Coloplasty Consulting fee Board membership; Uroplasty Consulting fee Consulting

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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