The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study was conducted in Finland as a joint project between the National Institute for Health and Welfare of Finland and the US National Cancer Institute (NCI) . The overall design, rationale, objectives, and initial results of this intervention study have been published1,2. Briefly, this was a randomized, double-blind, placebo-controlled, primary prevention trial to determine whether daily supplementation with alpha-tocopherol, beta-carotene, or both would reduce the incidence of lung or other cancers among male smokers.
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 groups based on a 2 x 2 factorial design. Men who had prior cancer or serious illness or who reported current use of vitamins E (>20 mg/day), A (>20,000 IU/day), or beta-carotene (>6 mg/day) were ineligible. Participants received either alpha-tocopherol (50 mg/day) as dl-alpha-tocopheryl acetate, beta-carotene (20 mg/day) as all-trans-beta-carotene, both supplements, or placebo capsules for 5-8 years (median 6.1 years) until death or trial closure (April 30, 1993).
The study was approved by the institutional review boards of the US National Cancer Institute and the National Institute for Health and Welfare of Finland, and written informed consent was obtained from each participant before randomization. Post-intervention follow-up continued through the Finnish Cancer Registry with data currently available through December 2012.
Cancer Case Identification
Incident cancers were defined based on the International Classification of Diseases 9. Medical records for each cancer case were reviewed centrally by one or two study physicians or oncologists to confirm the diagnoses. In addition, histopathological and cytological specimens available for 98 percent of the trial period cases were reviewed by two pathologists.
At baseline, study subjects completed a general risk factor, smoking, and medical history questionnaire, along with a food frequency (use) questionnaire, which consisted of a modified diet history, including both portion size and frequency of consumption for 203 food items and 73 mixed dishes3,4. This instrument was intended to measure usual consumption over the previous 12 months. Nutrient intake was estimated using food composition data available from the National Institute for Health and Welfare of Finland. Height, weight, blood pressure, heart rate, and visual acuity were measured.
Follow-up consisted of three visits annually to the local field center, 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 3 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 and Assays
Fasting serum samples were collected at the pre-randomization baseline visit, and stored at -70 degrees Celsius until assayed. At 3 years, the blood sampling was repeated for all participants. Close to the end of the intervention (during 1992-1993) a whole-blood sample was obtained. From the 2nd year of the trial onward, serum was also taken annually from a random sample of 700-800 participants.
The sera were analyzed for alpha-tocopherol, beta-carotene, retinol, and total and HDL cholesterol on all cohort subjects. Determinations of alpha-tocopherol, beta-carotene, and retinol were performed by high-performance liquid chromatography as described in Milne and Botnen, 19865. Serum cholesterol was determined enzymatically (CHOD-PAP method, Boehringer Mannheim).
The following other nutrients and biochemical factors have been measured on subsets of the cohort:
- Serum: folate, vitamin B6, vitamin B12, homocysteine, alpha-tocopherol, gamma-tocopherol, insulin, glucose, IGF, IGFBP-3, enterolactone, CD44, vitamin D, androstenedione, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), androstanediol glucuronide, prolactin, sex hormone-binding globulin, estradiol, and estrone, prothrombin antibodies, fatty acids, VEGF, ferritin, c-reactive protein, UIBC, TIBC, iron saturation, riboflavin, and flavin mononucleotide
- Toenails: selenium and arsenic
- Buccal mucosal cells: beta-carotene
Currently Available Data
- Number of Cancers Diagnosed Each Year by Organ Site (PDF)
- Number of Participants with Dietary Data and Biologic Specimens (PDF)
- The ATBC Cancer Prevention Study Group. The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann Epidemiol 1994 Han; 4(1):1-10. [View article (PDF)]
- 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;330(15):1029-35. [View article]
- 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. I. A self-administered food use questionnaire with a portion size picture booklet. Am J Epidemiol 1988 128(3):655-66. [View abstract]
- Pietinen P, Hartman AM, Haapa E, Rasanen L, Haapakoski J, Palmgren J, Albanes D, Virtamo J, Huttunen JK. Reproducilbility and validity of dietary assessment instruments. II. A qualitative food frequency questionnaire. Am J Epidemiol 1988 128(3):667-76.[View abstract]
- Milne DB, Botnen J. Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography. Clin Chem 1986 May;32(5):874-6. [View article (PDF)]
To view the PDF files on this site, you will need Adobe Acrobat Reader