Some 1,312 patients with a history of basal cell or squamous cell carcinoma of the skin were randomly assigned to receive, in double-blind fashion, 200 mcg/day of selenium (from high-selenium yeast [Nutrition 21]) or placebo. Patients were treated for a mean of 4.5 years, and the mean total follow-up period was 6.4 years. Selenium treatment did not affect the recurrence rate of skin cancers. However, compared with placebo, selenium treatment significantly reduced total cancer mortality (relative risk [RR] = 0.50; 95% CI, 0.31-0.80), total cancer incidence excluding skin cancers (RR = 0.63; 95% CI, 0.47-0.85), and the incidences of lung (RR = 0.54; 95% CI, 0.30-0.98), colorectal (RR = 0.42; 95% CI, 0.18-0.95), and prostate (RR = 0.37; 95% CI, 0.18-0.71) cancers. Selenium treatment also was associated with a nonsignificant 17% reduction in all-cause mortality. No cases of selenium toxicity occurred.
Comment: This study demonstrates a 37% reduction in total cancer incidence (excluding skin cancers) and a 50% reduction in total cancer mortality from the use of a selenium supplement for an average of 4.5 years. In addition, marked reductions were seen in the incidence of specific cancers (lung, colorectal, and prostate). A more recent follow-up study showed that selenium supplementation resulted in a 25% increase in the risk of squamous cell carcinoma in this cohort that already had had at least one previous episode of skin cancer (J Natl Cancer Inst 2003;95:1477-1481). Because squamous cell carcinoma is rarely fatal if treated early, that finding should not inhibit people from taking supplemental selenium to prevent more serious types of cancer. Individuals with a history of skin cancer who are taking selenium supplements should, of course, be closely followed by a dermatologist.
Since this study evaluated only people with a history of basal call or squamous cell carcinoma of the skin, it is not clear whether the results can be generalized to the rest of the population. Moreover, the reductions in cancer incidence and mortality described above were all secondary outcomes of the study, the primary outcome being the recurrence rate of non-melanoma skin cancers. Secondary outcomes are somewhat less reliable than primary outcomes, so another study should be designed specifically to test the hypothesis that selenium supplements prevent cancer and reduce cancer mortality.
The high-selenium yeast used in this study is sold under the trade name Selenomax. The chemical forms of selenium in yeast are complex, and not all of the selenium compounds have been identified. Therefore, one cannot assume that other forms of selenium (such as selenite, selenomethionine, or selenocysteine) would have the same benefits as high-selenium yeast.
Clark LC, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957-1963.
