ATBC Study Details
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 (formerly, National Public Health Institute) and the U.S. 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 (vitamin E), 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 intervention groups based on a 2×2 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 U.S. National Cancer Institute and the Finnish National Public Health Institute, and written informed consent was obtained from each participant before randomization. Post-intervention follow-up continued through the Finnish Cancer Registry and Statistics Finland with data currently available through December 2012.
Cancer Case Identification
Incident cancers were identified through linkage with the Finnish Cancer Registry, which provides nearly 100% ascertainment of cancer cases within Finland3,4. Cancers are defined based on the International Classification of Diseases 9. During the trial period (1985-1993) and post-trial period through 1999, 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% of the trial period 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 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 dishes5,6. 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 Public Health Institute of Finland. Height, weight, blood pressure, heart rate, and visual acuity were measured.
Follow-up consisted of three annual visits 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 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 and Assays
Fasting serum samples were collected at the pre-randomization baseline visit and stored at -80°C until assayed. At three 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 for germline DNA. From the second year of the trial onward, serum was also 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. Determinations of alpha-tocopherol, beta-carotene, and retinol were performed by reversed-phase high-performance liquid chromatography as described in Milne and Botnen, 19867. Serum cholesterol was determined enzymatically (CHOD-PAP method, Boehringer Mannheim).
The following nutrients and biomarkers have been measured for subsets of the cohort:
- Serum: folate, vitamin B6, vitamin B12, homocysteine, alpha-tocopherol, gamma-tocopherol, insulin, glucose, IGF, IGFBP-3, enterolactone, CD44, vitamin D, vitamin D binding protein, androstenedione, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), androstanediol glucuronide, prolactin, sex hormone-binding globulin (SHBG), estradiol, estrone, prothrombin antibodies, fatty acids, VEGF, ferritin, C-reactive protein, UIBC, TIBC, iron saturation, riboflavin, flavin mononucleotide, creatinine, gastrin, cholecystokinin, pepsinogen, PSA, sarcosine, antiparietal cell and anti-intrinsic factor antibodies, thyroxine, thyroid hormones, H. pylori, adiponectin, leptin, ghrelin, bile acids, TMAO, short-chain fatty acids, immunoglobulins, proteomics, lipdomics and metabolomics
- Toenails: selenium, arsenic and other trace metals
- 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)
References
- 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]
- 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]
- Korhonen P, Malila N, Pukkala E, Teppo L, Albanes D, Virtamo J. The Finnish Cancer Registry as follow-up source of a large trial cohort–accuracy and delay. Acta Oncol 2002;41(4):381-8. [View article]
- Leinonen MK, Miettinen J, Heikkinen S, Pitkäniemi J, Malila N. Quality measures of the population-based Finnish Cancer Registry indicate sound data quality for solid malignant tumours. Eur J Cancer 2017 May;77:31-39. [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 article]
- 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 article]
- 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]
To view the PDF files on this site, you will need Adobe Acrobat Reader