EFFECTS OF SELENIUM SUPPLEMENTATION FOR CANCER PREVENTION IN PATIENTSWITH CARCINOMA OF THE SKIN A RANDOMIZED CONTROLLED TRIAL - A RANDOMIZED CONTROLLED TRIAL

Objective.-To determine whether a nutritional supplement of selenium w ill decrease the incidence of cancer. Design.-A multicenter, double-bl ind, randomized, placebo-controlled cancer prevention trial. Setting.- Seven dermatology clinics in the eastern United States. Patients. A to tal of 1312 patients (mean age, 63 years; range, 18-80 years) with a h istory of basal cell or squamous cell carcinomas of the skin were rand omized from 1983 through 1991. Patients were treated for a mean (SD) o f 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interv entions.-Oral administration of 200 mu g of selenium per day or placeb o.Main Outcome Measures.-The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The sec ondary end points, established in 1990, were all-cause mortality and t otal cancer mortality, total cancer incidence, and the incidences of l ung, prostate, and colorectal cancers. Results.-After a total follow-u p of 8271 person-years, selenium treatment did not significantly affec t the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the seleniu m group and 350 cases among the control group (relative risk [RR], 1.1 0; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls ( RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points reveale d that, compared with controls, patients treated with selenium had a n onsignificant reduction in all-cause mortality (108 deaths in the sele nium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63 -1.08]) and significant reductions in total cancer mortality (29 death s in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the seleni um group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incid ences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer inc idence in the selenium group, the blinded phase of the trial was stopp ed early. No cases of selenium toxicity occurred. Conclusions.-Seleniu m treatment did not protect against development of basal or squamous c ell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. The se effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.