Taylor P R, Li B, Dawsey S M, Li J Y, Yang C S, Guo W, Blot W J
National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1994 Apr 1;54(7 Suppl):2029s-2031s.
In Linxian China, the esophageal/gastric cardia cancer mortality rates are among the highest in the world. There is suspicion that the population's chronic deficiencies of multiple micronutrients are etiologically involved. We conducted two randomized, placebo-controlled nutrition intervention trials to test the effects of vitamin and mineral supplements in lowering the rates of esophageal/gastric cancer. In the first trial, the dysplasia trial, 3318 adults with a cytological diagnosis of esophageal dysplasia received daily supplementation with 26 vitamins and minerals in doses typically 2-3 times the United States Recommended Daily Allowances, or placebos, for 6 years. The second trial, the general population trial, involved 29,584 adults and used a one-half replicate of a 2(4) factorial experimental design which tested the effects of four combinations of nutrients: A, retinol and zinc; B, riboflavin and niacin; C, vitamin C and molybdenum; and D, beta-carotene, vitamin E, and selenium. Doses for these daily supplements ranged from 1 to 2 times the United States Recommended Daily Allowances, and the different vitamin/mineral combinations or placebos were taken for a period of 5.25 years. As part of the general population trial, and end-of-intervention endoscopy survey was carried out in a small (1.3%) sample of subjects to see if supplementation affected the prevalence of dysplasia and early cancer. Herein we review the methods of these trials and the results of the endoscopic survey. Fifteen esophageal and 16 gastric cancers were identified in endoscopic biopsies from the 391 subjects evaluated from two villages, and nearly all were asymptomatic. No significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the four supplement groups. However, the prevalence of gastric cancer among participants receiving retinol and zinc was 62% lower than those not receiving those supplements (P = 0.09), while participants receiving beta-carotene, vitamin E, and selenium had a 42% reduction in esophageal cancer prevalence (0.34). We have reported separately that cancer mortality over the entire 5.25-year period was significantly reduced among those receiving beta-carotene, vitamin E, and selenium. The findings from the overall trial and the endoscopic sample offer a hopeful sign and should encourage additional studies with these agents in larger numbers of subjects.
在中国林县，食管癌和贲门癌的死亡率位居世界前列。人们怀疑人群中多种微量营养素的长期缺乏在病因学上起到了作用。我们开展了两项随机、安慰剂对照的营养干预试验，以测试维生素和矿物质补充剂对降低食管癌和胃癌发病率的效果。在第一项试验即发育异常试验中，3318名经细胞学诊断为食管发育异常的成年人，每天接受26种维生素和矿物质的补充，剂量通常是美国推荐每日摄入量的2至3倍，或者服用安慰剂，持续6年。第二项试验即普通人群试验，涉及29584名成年人，采用了2(4)析因实验设计的一半重复，测试了四种营养素组合的效果：A组，视黄醇和锌；B组，核黄素和烟酸；C组，维生素C和钼；D组，β-胡萝卜素、维生素E和硒。这些每日补充剂的剂量为美国推荐每日摄入量的1至2倍，不同的维生素/矿物质组合或安慰剂服用5.25年。作为普通人群试验的一部分，对一小部分（1.3%）受试者进行了干预结束时的内镜检查，以观察补充剂是否影响发育异常和早期癌症的患病率。在此，我们回顾这些试验的方法以及内镜检查的结果。在对来自两个村庄的391名受试者进行的内镜活检中，发现了15例食管癌和16例胃癌，几乎所有患者都没有症状。四个补充剂组中，食管或胃发育异常或癌症的患病率均未出现显著降低。然而，接受视黄醇和锌的参与者中胃癌患病率比未接受这些补充剂的参与者低62%（P = 0.09），而接受β-胡萝卜素、维生素E和硒的参与者食管癌患病率降低了42%（0.34）。我们已单独报道，在接受β-胡萝卜素、维生素E和硒的人群中，整个5.25年期间的癌症死亡率显著降低。总体试验和内镜样本的研究结果提供了一个充满希望的信号，应该鼓励对更多受试者使用这些药物进行进一步研究。
