Omenn G S, Goodman G E, Thornquist M D, Balmes J, Cullen M R, Glass A, Keogh J P, Meyskens F L, Valanis B, Williams J H, Barnhart S, Hammar S
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
N Engl J Med. 1996 May 2;334(18):1150-5. doi: 10.1056/NEJM199605023341802.
Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.
We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.
A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.
After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
肺癌和心血管疾病是美国主要的死亡原因。有人提出类胡萝卜素和视黄醇可能是预防这些疾病的物质。
我们进行了一项多中心、随机、双盲、安慰剂对照的一级预防试验——β-胡萝卜素与视黄醇功效试验，共纳入18314名吸烟者、既往吸烟者和接触石棉的工人。将每天30毫克β-胡萝卜素与25000国际单位视黄醇（维生素A）以棕榈酸视黄酯形式联合使用对主要终点——肺癌发病率的影响与安慰剂进行比较。
在73135人年的随访期间（平均随访时间4.0年），共诊断出388例新肺癌病例。与安慰剂组相比，活性治疗组肺癌的相对风险为1.28（95%置信区间为1.04至1.57；P = 0.02）。其他类型癌症的风险无统计学显著差异。在活性治疗组中，任何原因导致的死亡相对风险为1.17（95%置信区间为1.03至1.33）；肺癌死亡相对风险为1.46（95%置信区间为1.07至2.00）；心血管疾病死亡相对风险为1.26（95%置信区间为0.99至1.61）。基于这些发现，随机试验比计划提前21个月停止；随访将再持续5年。
平均补充四年后，β-胡萝卜素和维生素A联合使用对肺癌发病率以及吸烟者和接触石棉工人的肺癌、心血管疾病及任何原因导致的死亡风险没有益处，甚至可能有不利影响。
