Overview
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was a cancer prevention trial conducted by the U.S. National Cancer Institute (NCI) and National Public Health Institute of Finland, which later became the National Institute for Health and Welfare, from 1985 to 1993. The purpose of the ATBC study was to determine whether specific vitamin supplements prevented lung cancer and other cancers in smokers.
Data from participants have contributed to critical findings many consortia studying nutritional and other environmental factors and cancer risk, biomarkers, candidate genes and pathway analyses, and genome-wide association studies. These include investigations into etiology of colorectal, lung, prostate and biliary tract cancers; metabolomic studies; HPV-associated cancers; genetic studies of the above malignancies and studies of pancreatic, brain, and lymphoid malignancies; and prospective studies of diet and cancer.
Study Team
NCI Lead Investigator
Demetrius Albanes, M.D., senior investigator, Metabolic Epidemiology Branch
National Institute for Health and Welfare Investigators
Satu Männistö, PhD
Jarmo Virtamo, MD, PhD
Finnish Cancer Registry and Society Investigators
Nea Malila, MD, PhD
Matti Rautalahti, MD, PhD
Background & Purpose
The ATBC study was an integral research resource for NCI for nearly three decades. It was designed to test hypotheses based on epidemiological and experimental evidence supporting nutritional interventions to prevent cancer, including lower risk among persons with higher vitamin status and vegetable consumption, and the biological and anti-neoplastic properties of several antioxidants and micronutrients.
Study Design
A total of 29,133 men between the ages of 50 and 69 years, who smoked at least five cigarettes per day, were recruited from southwestern Finland between 1985 and 1988, and randomly assigned to one of four intervention groups. Men who had prior cancer or serious illness or who reported current use of certain vitamins were ineligible. Participants received either alpha-tocopherol, beta-carotene, both supplements, or placebo capsules for 5-8 years (median 6.1 years) until death or trial closure (April 30, 1993). Post-intervention follow-up continued through the Finnish Cancer Registry and Statistics Finland with follow-up data through 2012.
Histopathological and cytological specimens (available for 98% of cases) were reviewed by two pathologists. Medical records were reviewed annually for a subset of cases diagnosed after 1999. In total, medical record reviews were conducted for 59% of cancer cases overall.
Data Collection
At baseline, study participants completed a questionnaire on risk factors, smoking, and medical history, a food frequency questionnaire, and were measured for height, weight, blood pressure, heart rate, and visual acuity. Follow-up consisted of three annual visits, during which the men were asked about their health, use of non-trial vitamin supplements, and smoking habits since the last visit. Height, weight, blood pressure, heart rate, and visual acuity were measured once a year. At three years, the food frequency questionnaire was repeated for all participants.
Participants in the study were asked to contact their local study center as soon as possible if they were diagnosed with cancer, and they were then invited for a follow-up visit, where they completed another food frequency questionnaire.
Biological Specimen Collection
Fasting serum samples were collected at the pre-randomization baseline visit and year three; a whole-blood sample was obtained for germline DNA. From the second year onward, serum was taken annually from a random sample of 700-800 participants. The baseline and three-year sera were analyzed for alpha-tocopherol, beta-carotene, retinol, and total and HDL cholesterol in all cohort subjects. The study measured multiple nutrients and biomarkers for subsets of the cohort.
Select Results & Publications
Findings from the Clinical Trial
The investigators found 8% higher overall mortality and 18% increased lung cancer incidence in the β-carotene arm, and 32% lower prostate cancer incidence in the men supplemented with vitamin E.
- The ATBC Cancer Prevention Study Group. The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol. 1994.
- The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994.
- Korhonen P, et al. The Finnish Cancer Registry as follow-up source of a large trial cohort–accuracy and delay. Acta Oncol. 2002.
- Leinonen MK, et al. Quality measures of the population-based Finnish Cancer Registry indicate sound data quality for solid malignant tumours. Eur J Cancer. 2017.
- Pietinen P, et al. Reproducibility and validity of dietary assessment instruments. I. A self-administered food use questionnaire with a portion size picture booklet. Am J Epidemiol. 1988.
- Pietinen P, Hartman AM, Haapa E, Rasanen L, Haapakoski J, Palmgren J, Albanes D, Virtamo J, Huttunen JK. Reproducibility and validity of dietary assessment instruments. II. A qualitative food frequency questionnaire. Am J Epidemiol. 1988.
- Milne DB, Botnen J. Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography. Clin Chem. 1986.
Additional Research in ATBC
- Gutiérrez-Torres DS. et al. Changes in smoking use and subsequent lung cancer risk in the ATBC Study. JNCI. 2024.
Data Sharing
Research groups seeking to utilize ATBC data can submit proposals for collaboration to the NCI or THL Principal Investigators, Dr. Demetrius Albanes and Dr. Satu Männistö, respectively. They are scientifically reviewed at either institution.
Timeliness, research priority, study design, consideration of unique characteristics of the ATBC Study cohort, and judicious utilization of limited biospecimens are factors relevant to consideration of any proposed research and hypothesis testing.
Approved studies must receive appropriate review at the collaborating institution. Periodic study progress reports are required; analyses not completed within one year of the originally proposed date may be reassigned.