Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group.

OBJECTIVE: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. DESIGN: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. SETTING: Seven dermatology clinics in the eastern United States. PATIENTS: A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. INTERVENTIONS: Oral administration of 200 microg of selenium per day or placebo. MAIN OUTCOME MEASURES: The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. RESULTS: After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 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 revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium 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 deaths 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 selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. CONCLUSIONS: Selenium treatment did not protect against development of basal or squamous cell 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. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made

Circadian rhythms and differences in epidermal and in dermal cel proliferation in uninvolved and involved psoriatic skin in vivo.

Using in vivo DNA labeling procedures, the present study makes a detailed comparative analysis of circadian rhythms in labeling indexes (Is), in mitotic indexes (Im), and in Is/Im ratios in uninvolved and in involved psoriatic epidermis in vivo (12 patients, studied at 6-hr intervals over a 24-hr period). We also provide comparable data on the rates of epidermal DNA synthesis and on the proliferative activity of dermal infiltrate cells. There are no circadian-diurnal variations in epidermal or in dermal infiltrate cell proliferation in either inactive (uninvolved) or in active (involved) lesions of psoriatic skin. The rates of epidermal DNA synthesis were lower at 9 AM and 3 PM; higher at 9 PM and 3 AM in both uninvolved and involved epidermis. The following cell kinetic information was derived from 78 biopsy samples-from epidermal mitotic and labeled nuclei counts in approximately 100 mm unit lengths of epidermis per biopsy. DNA labeling indexes, 6.1 vs. 21.2%; mitotic indexes, 0.13 vs. 0.43%; and Is/Im ratios, 152/1 vs 70/1 in uninvolved vs. involved psoriatic epidermis in vivo. There was an overall 20% decrease in the rate of cycling epidermal cell DNA synthesis involved epidermis; and 5-fold increase in the overall proliferative activity of dermal infiltrate cells in involved psoriatic skin. These results are discussed in relation to the clinical use of circadian rhythms for the "chronotherapy" of proliferative diseases in man, in relation to cell cycle aspects of psoriasis and psoriatic epidermal responses to therapy, and in relation to cell proliferation in human epidermis in vivo.