Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study

α-生育酚、β-胡萝卜素癌症预防 (ATBC) 研究

• 批准号: 8349590
• 负责人: Demetrius Albanes
• 金额: $ 122.31万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349590
• 关键词: Adverse effects; Age; All-Trans-Retinol; Antioxidants; Area; Beta Carotene; Binding Sites; Biochemical; Biochemical Genetics; Biological; Biological Markers; Bladder; Bronchi; Carbon; Carotene; Carotenoids; Categories; Caucasians; Caucasoid Race; Cessation of life; Chest; Cigarette; Cohort Analysis; Cohort Studies; Collaborations; Colon; Colorectal; Colorectal Cancer; Data; Diagnosis; Diet; Dietary Questionnaires; Dimensions; Disease; Effectiveness; Epidemiology; Erythrocytes; Evaluation; Extramural Activities; Film; Finland; Folate; Food; Freezing; Genetic Polymorphism; Genetic Variation; Genotype; Glioma; Goals; Gonadal Steroid Hormones; Growth Factor; Habits; Head and neck structure; Health; High Density Lipoprotein Cholesterol; Human; Human Resources; Institutes; Insulin; International; Intervention; Investigation; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Measurement; Medical; Medical Records; Metabolism; Molecular; National Cancer Institute; Nested Case-Control Study; Nutrient; Nutritional; Occupational; Other Genetics; Pancreas; Participant; Pathology; Phase; Phenotype; Placebos; Pleura; Population Registers; Procedures; Prospective Studies; Prostate; Public Health; Randomized; Randomized Controlled Trials; Recruitment Activity; Rectum; Renal carcinoma; Research; Research Personnel; Research Project Grants; Resources; Risk; Sampling; Selenium; Serum; Slide; Smoker; Smoking; Specialized Center; Specimen; Structure of base of prostate; Structure of nail of toe; Supplementation; Surveys; Testing; Tocopherols; Trachea; Visit; Vitamin D; Vitamin E; Vitamin E Acetate; Vitamins; Whole Blood; abstracting; alpha Tocopherol; base; cancer prevention; capsule; case control; cohort; design; diet and cancer; energy balance; follow-up; genetic variant; genome wide association study; group intervention; interest; intervention effect; male; malignant breast neoplasm; malignant stomach neoplasm; men; neoplasm registry; nutrition; population based; post intervention; prevent; web site

The ATBC Cohort Follow-up Study has been in place since 1994. Male smokers between the ages of 50 and 69 were recruited from southwestern Finland between April 1985 and June 1988. A total of 29,133 men were randomly assigned to one of four intervention groups: 50 mg/day a-tocopherol (as dl-a-tocopheryl acetate); 20 mg/day b-carotene; both a-tocopherol and b-carotene; or placebo. They were followed for five to eight years during the trial, until death, or 30 April 1993 when intervention was stopped (median follow-up, 6.1 years). Follow-up for endpoints was continued postinterventionFollowing invitation for participation and recruitment through a population-based postal survey, the trial randomly assigned 29,133 Caucasian 50-69 year old male smokers of >5 cigarettes daily to one of four intervention groups based on a 2x2 factorial design: -carotene (20 mg/day), vitamin E (50 mg/day, as dl--tocopheryl acetate), both agents, or placebo. At entry, medical, dietary, smoking, and occupational data were obtained, along with physical measurements, a chest x-ray, and serum and toenail samples. Diet was captured through a 276 food item dietary questionnaire that was developed and validated for the trial. Baseline serum was collected, frozen, and stored for all participants, and vitamin E, beta-carotene, retinol, and total and HDL cholesterol were determined. Follow-up serum and whole blood were collected for all active participants later in the study, as were additional serum and red blood cell samples from selected subsets. Active intervention continued for 5-8 years, with three study visits annually during which participants were asked about their health and possible subjective side effects, capsule compliance, and smoking habits since the last visit. Chest films were taken at 2-3 year intervals and at the end of the trial. All incident cancers were identified through the nationwide Finnish Cancer Registry, medical records/pathology slides were reviewed / abstracted, and deaths/underlying causes were identified through the National Population Register. The ATBC Cohort Follow-up Study has had the overall aim of conducting cancer etiologic research and post-intervention cancer surveillance based on the original trial cohort of 29,133 men. Cohort analyses, nested case-control investigations, analyses of genetic polymorphisms and other molecular parameters, and studies of the biological effects of the intervention agents on relevant biomarkers have been conducted and are the focus of ongoing research. Current cumulative totals of diagnosed cases through 2005 include approximately 2,800 lung, 2,000 prostate, 700 colorectal, 500 bladder, 300-400 each for stomach, pancreas, and kidney cancers, 300 head and neck, and 1,100 for other sites combined. Cancer etiologic research in the ATBC Study has evolved naturally from the focus on supplementation into several areas of concentration that reflect both our research interests and the availability of study resources to a continually growing number of highly productive investigators both at NCI and elsewhere. A public website (http://dceg.cancer.gov/atbcstudy) provides information regarding the projects research, data, personnel, and resources, including procedures for initiating collaborations. The high-quality study data, biological specimens, and ongoing endpoint ascertainment have been applied to testing biochemical and genetic hypotheses related to nutritional and other factors having potentially high attributable risks in prostate (based on 2,500 cases), lung (3,500 cases), colorectal (700 cases), pancreatic (>400 cases) and other cancers. GWAS studies of risk for prostate, lung, renal, and bladder cancers, as well as NHL and glioma are completed. We have completed investigations of vitamins D, E, A and selenium status; carotenoids and other antioxidants; one-carbon metabolism; energy balance, insulin, and growth factors; sex steroids; and genetic variants impacting these exposures. GWAS studies of nutrition phenotypes such as serum vitamin D status are being conducted. Evaluation of these factors within the context of the controlled vitamin supplementation design has afforded us unique opportunities to investigate biological and biochemical interactions. Another important dimension of the ATBC Study has been collaborations with extramural researchers in cancer epidemiological consortia. These include: the NCI Breast and Prostate Cancer Cohort Consortium (BPC3), PanScan, the Pooling Project of Prospective Studies of Diet and Cancer, and the Harvard Specialized Center on Folate, One-Carbon Nutrients, Gene Variants and Colorectal Cancer. We contribute scientific expertise, data and cohort resources, and intramural support to these powerful, high-impact studies.

ATBC队列随访研究自1994年以来一直在进行。1985年4月至1988年6月期间，从芬兰西南部招募了50至69岁的男性吸烟者。共有29，133名男性被随机分配到四个干预组之一：50 mg/天a-生育酚（作为dl-a-生育酚乙酸酯）; 20 mg/天b-胡萝卜素; a-生育酚和b-胡萝卜素;或安慰剂。在试验期间，他们被随访了5 - 8年，直到死亡，或1993年4月30日停止干预（中位随访时间为6.1年）。在通过基于人群的邮寄调查邀请参与和招募之后，该试验将29，133名每天吸烟>5支的高加索50-69岁男性吸烟者随机分配到基于2x2析因设计的四个干预组之一：- 胡萝卜素（20 mg/天）、维生素E（50 mg/天，以dl-生育酚乙酸酯形式）、两种药剂或安慰剂。在进入时，医疗，饮食，吸烟和职业数据，沿着与物理测量，胸部X光片，血清和脚趾甲样品。通过为试验开发和验证的276种食物的饮食调查问卷获取饮食。收集、冷冻并储存所有参与者的基线血清，并测定维生素E、β-胡萝卜素、视黄醇、总胆固醇和HDL胆固醇。在研究后期采集所有活跃参与者的随访血清和全血，以及来自选定子集的额外血清和红细胞样本。积极干预持续5-8年，每年进行三次研究访视，在此期间，参与者被问及自上次访视以来的健康状况和可能的主观副作用，胶囊依从性和吸烟习惯。每隔2-3年和试验结束时拍摄胸片。通过全国范围的芬兰癌症登记处确定所有癌症事件，审查/提取医疗记录/病理切片，并通过国家人口登记处确定死亡/根本原因。ATBC队列随访研究的总体目标是基于29，133名男性的原始试验队列进行癌症病因学研究和干预后癌症监测。已经进行了队列分析、巢式病例对照调查、遗传多态性和其他分子参数分析以及干预剂对相关生物标志物的生物效应研究，这些都是正在进行的研究的重点。截至2005年，目前累计确诊病例包括约2,800例肺癌，2,000例前列腺癌，700例结肠直肠癌，500例膀胱癌，胃癌、胰腺癌和肾癌各300-400例，头颈癌300例，其他部位合计1,100例。ATBC研究中的癌症病因学研究已经从关注补充剂自然演变为几个集中领域，这些领域反映了我们的研究兴趣和研究资源的可用性，以不断增加NCI和其他地方的高产研究人员。一个公共网站（http：//dceg.cancer.gov/atbcstudy）提供有关项目研究、数据、人员和资源的信息，包括启动合作的程序。高质量的研究数据、生物标本和正在进行的终点确定已被应用于检验与营养和其他因素相关的生化和遗传假设，这些因素在前列腺癌（基于2,500例病例）、肺癌（3,500例病例）、结直肠癌（700例病例）、胰腺癌（>400例病例）和其他癌症中具有潜在的高归因风险。GWAS对前列腺癌、肺癌、肾癌和膀胱癌以及NHL和神经胶质瘤风险的研究已经完成。我们已经完成了对维生素D，E，A和硒状态的调查;类胡萝卜素和其他抗氧化剂;一碳代谢;能量平衡，胰岛素和生长因子;性类固醇;以及影响这些暴露的遗传变异。正在进行GWAS营养表型研究，如血清维生素D状态。在控制维生素补充设计的背景下，这些因素的评价为我们提供了独特的机会，研究生物和生化相互作用。ATBC研究的另一个重要方面是与癌症流行病学联盟的校外研究人员合作。其中包括：NCI乳腺癌和前列腺癌队列研究联盟（BPC 3）、PanScan、饮食和癌症前瞻性研究汇集项目和哈佛叶酸、一碳营养素、基因变异和结直肠癌专业中心。我们贡献科学专业知识，数据和队列资源，并为这些强大的，高影响力的研究提供校内支持。