Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and Cohort Follow-up

目的：该项目调查补充维生素E或β-胡萝卜素是否会降低肺癌，前列腺癌和其他癌症的发病率，并在一个大型的前瞻性队列中测试与癌症预防，病因学（包括基因-环境相互作用）和早期检测相关的几个假设。背景技术背景：研究表明，某些微量营养素，包括维生素E和β-胡萝卜素，基于抗氧化剂，抗增殖和其他特性，在癌症预防中发挥作用。方法：ATBC研究是一项随机对照干预试验，每天补充β-胡萝卜素（20 mg）和/或维生素E（50 mg dl-α-生育酚乙酸酯）5-8年。29，133名参与者是芬兰西南部50-69岁的男性吸烟者。在基线时收集血清、脚趾甲和问卷调查数据，并在随访期间收集血清、全血和RBC。所有癌症每年都通过国家癌症登记处进行鉴定，并进行中央医疗记录和病理学审查。进展：积极干预于1993年结束，并继续随访队列检查试验后的发病率趋势。 队列和巢式病例对照研究正在进行中，包括许多旨在测试环境基因（即多态性）假设的研究。干预研究结果显示，维生素E组前列腺癌（32%）和结直肠癌（22%）的发病率降低，主要心血管事件略有减少。β-胡萝卜素没有预防癌症的作用，并导致肺癌发病率（16%）和总死亡率（8%）增加。器官特异性干预和癌症病因学分析集中在广泛的假设上，这些假设利用随机干预、基线风险因素数据和前瞻性收集的生物标本（血清、DNA等）。 研究问题包括，例如，维生素E，硒，类胡萝卜素，叶酸/同型半胱氨酸，维生素D，酒精和其他饮食成分，类固醇激素，体力活动和血清微量营养素浓度对癌症的影响。 还正在研究的是两种试验药物的作用机制（特别是维生素E，考虑到观察到的前列腺化学预防作用），以及几种遗传多态性和DNA标记物（包括GST、CYP、NQO 1、叶酸和甲基代谢、IGF、雄激素代谢、维生素D受体和DNA损伤和修复）的癌症风险关系。

OBJECTIVE: This project investigates whether supplementation with vitamin E or beta-carotene reduces incidence of lung, prostate, and other cancers, and tests several hypotheses related to cancer prevention, etiology (including gene-environment interactions), and early detection in a large, prospective cohort. BACKGROUND: Research indicates a role in cancer prevention for certain micronutrients, including vitamin E and beta-carotene, based on antioxidant, antiproliferative, and other properties. METHODS: The ATBC Study is a randomized, controlled intervention trial of daily supplementation with beta-carotene (20 mg) and/or vitamin E (50 mg dl-alpha-tocopheryl acetate) for 5-8 years. The 29,133 participants are 50-69 year old male cigarette smokers in southwestern Finland. Serum, toenails, and questionnaire data were collected at baseline, and serum, whole blood, and RBC's during followup. All cancers are identified annually through the national cancer registry, with central medical record and pathology reviews. PROGRESS: Active intervention concluded in 1993, and continued follow-up of the cohort examines post-trial incidence trends. Cohort and nested case-control investigations are underway, including many aimed at testing environmental-gene (ie, polymorphism) hypotheses. Intervention findings showed reduced incidence in the vitamin E group for prostate (32%) and colorectal (22%) cancers, and modest reductions in major cardiovascular events. Beta-carotene demonstrated no cancer preventive effects and resulted in increased lung cancer incidence (16%) and overall mortality (8%). Organ-specific intervention and cancer etiologic analyses are focused on a wide range of hypotheses that utilize the randomized interventions, baseline risk factor data, and prospectively collected biospecimens (serum, DNA, etc.). The research questions include, for example, effects of vitamin E, selenium, carotenoids, folate/homocysteine, vitamin D, alcohol, and other dietary components, steroid hormones, physical activity, and serum micronutrient concentrations on cancer. Also being investigated are mechanisms through which the two trial agents acted (and vitamin E in particular, given the prostate chemopreventive effect observed), and the cancer risk relation of several genetic polymorphisms and DNA markers including those for GSTs, CYPs, NQO1, folate and methyl-group metabolism, IGF's, androgen metabolism, vitamin D receptors, and DNA damage and repair.