Clark L C, Combs G F, Turnbull B W, Slate E H, Chalker D K, Chow J, Davis L S, Glover R A, Graham G F, Gross E G, Krongrad A, Lesher J L, Park H K, Sanders B B, Smith C L, Taylor J R
Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, USA.
JAMA. 1996 Dec 25;276(24):1957-63.
To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.
A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.
Seven dermatology clinics in the eastern United States.
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.
Oral administration of 200 microg of selenium per day or placebo.
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.
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.
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
确定补充硒营养剂是否会降低癌症发病率。
一项多中心、双盲、随机、安慰剂对照的癌症预防试验。
美国东部的七家皮肤科诊所。
1983年至1991年期间，共有1312例有皮肤基底细胞癌或鳞状细胞癌病史的患者（平均年龄63岁；范围18 - 80岁）被随机分组。患者平均接受治疗4.5（2.8）年，总随访时间为6.4（2.0）年。
每天口服200微克硒或安慰剂。
该试验的主要终点是皮肤基底细胞癌和鳞状细胞癌的发病率。1990年确定的次要终点是全因死亡率、总癌症死亡率、总癌症发病率以及肺癌、前列腺癌和结直肠癌的发病率。
在总计8271人年的随访后，硒治疗对皮肤基底细胞癌或鳞状细胞癌的发病率没有显著影响。硒组有377例新的基底细胞皮肤癌病例，对照组有350例（相对风险[RR]，1.10；95%置信区间[CI]，0.95 - 1.28），硒组有218例新的鳞状细胞皮肤癌病例，对照组有190例（RR，1.14；95%CI，0.93 - 1.39）。次要终点分析显示，与对照组相比，接受硒治疗的患者全因死亡率有非显著降低（硒组108例死亡，对照组129例死亡[RR；0.83；95%CI，0.63 - 1.08]），总癌症死亡率有显著降低（硒治疗组29例死亡，对照组57例死亡[RR，0.50；95%CI，0.31 - 0.80]），总癌症发病率有显著降低（硒组77例癌症，对照组119例[RR，0.63；95%CI，0.47 - 0.85]），以及肺癌、结直肠癌和前列腺癌的发病率有显著降低。主要由于硒组总癌症死亡率和总癌症发病率明显降低，该试验的盲法阶段提前终止。未发生硒中毒病例。
硒治疗不能预防皮肤基底细胞癌或鳞状细胞癌的发生。然而，次要终点分析结果支持以下假设，即补充硒可能降低多个部位癌症的发病率和死亡率。在能够就补充硒提出新公共卫生建议之前，硒的这些作用需要在一项设计适当的独立试验中得到证实。
