This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Men's Health  • Prostate Disease  • Oncology  • Lung Cancer  • Prostate Cancer  • Pulmonary Diseases  • Pulmonary Diseases, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Incidence of Cancer and Mortality Following -Tocopherol and -Carotene Supplementation

A Postintervention Follow-up

The ATBC Study Group

JAMA. 2003;290:476-485.

Context  In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, -tocopherol supplementation decreased prostate cancer incidence, whereas -carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.

Objective  To analyze postintervention effects of -tocopherol and -carotene on cancer incidence and total and cause-specific mortality.

Design, Setting, and Participants  Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received -tocopherol (50 mg), -carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.

Main Outcome Measures  Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.

Results  Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of -carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving -tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for -tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for -carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for -carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.

Conclusions  The beneficial and adverse effects of supplemental -tocopherol and -carotene disappeared during postintervention follow-up. The preventive effects of -tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid -carotene supplementation.

ATBC Study Group Authors: Jarmo Virtamo, MD, Pirjo Pietinen, DSc, Jussi K. Huttunen, MD, Pasi Korhonen, PhD, Nea Malila, MD, and Mikko J. Virtanen, MSc, National Public Health Institute, Helsinki, Finland; Demetrius Albanes, MD, Phil R. Taylor, MD, and Paul Albert, PhD, National Cancer Institute, Bethesda, Md.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Associations between {alpha}-Tocopherol, {beta}-Carotene, and Retinol and Prostate Cancer Survival
Watters et al.
Cancer Res. 2009;69:3833-3841.
ABSTRACT | FULL TEXT  

Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial
Qiao et al.
JNCI J Natl Cancer Inst 2009;101:507-518.
ABSTRACT | FULL TEXT  

Bayesian model averaging in meta-analysis: vitamin E supplementation and mortality
Berry et al.
Clin Trials 2009;6:28-41.
ABSTRACT  

Vitamin E intake, {alpha}-tocopherol status, and pancreatic cancer in a cohort of male smokers
Stolzenberg-Solomon et al.
Am. J. Clin. Nutr. 2009;89:584-591.
ABSTRACT | FULL TEXT  

Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial
Gaziano et al.
JAMA 2009;301:52-62.
ABSTRACT | FULL TEXT  

Carotenoids and the risk of developing lung cancer: a systematic review
Gallicchio et al.
Am. J. Clin. Nutr. 2008;88:372-383.
ABSTRACT | FULL TEXT  

Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer
Slatore et al.
Am. J. Respir. Crit. Care Med. 2008;177:524-530.
ABSTRACT | FULL TEXT  

Efficacy of Antioxidant Supplementation in Reducing Primary Cancer Incidence and Mortality: Systematic Review and Meta-analysis
Bardia et al.
Mayo Clin Proc. 2008;83:23-34.
ABSTRACT | FULL TEXT  

A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men: The Physicians' Health Study II
Grodstein et al.
Arch Intern Med 2007;167:2184-2190.
ABSTRACT | FULL TEXT  

Pharmacological and Chemical Effects of Cigarette Additives
Rabinoff et al.
Am. J. Public Health 2007;97:1981-1991.
ABSTRACT | FULL TEXT  

Plasma carotenoids, retinol, and tocopherols and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition study
Key et al.
Am. J. Clin. Nutr. 2007;86:672-681.
ABSTRACT | FULL TEXT  

Beta Carotene Supplementation and Age-Related Maculopathy in a Randomized Trial of US Physicians
Christen et al.
Arch Ophthalmol 2007;125:333-339.
ABSTRACT | FULL TEXT  

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis
Bjelakovic et al.
JAMA 2007;297:842-857.
ABSTRACT | FULL TEXT  

Vitamin and mineral supplements for cancer prevention: issues and evidence
Fairfield and Stampfer
Am. J. Clin. Nutr. 2007;85:289S-292S.
ABSTRACT | FULL TEXT  

Clinical trials of vitamin and mineral supplements for cancer prevention
Greenwald et al.
Am. J. Clin. Nutr. 2007;85:314S-317S.
ABSTRACT | FULL TEXT  

Statistical Models for Causation: What Inferential Leverage Do They Provide?
Freedman
Eval Rev 2006;30:691-713.
ABSTRACT  

Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.
Wright et al.
Am. J. Clin. Nutr. 2006;84:1200-1207.
ABSTRACT | FULL TEXT  

Prospective Study of Fruits and Vegetables and Risk of Oral Premalignant Lesions in Men
Maserejian et al.
Am J Epidemiol 2006;164:556-566.
ABSTRACT | FULL TEXT  

American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer With Healthy Food Choices and Physical Activity
Kushi et al.
CA Cancer J Clin 2006;56:254-281.
ABSTRACT | FULL TEXT  

Enhanced tumorigenesis in p53 knockout mice exposed in utero to high-dose vitamin E
Chen and Wells
Carcinogenesis 2006;27:1358-1368.
ABSTRACT | FULL TEXT  

Carotenoids and cardiovascular health
Voutilainen et al.
Am. J. Clin. Nutr. 2006;83:1265-1271.
ABSTRACT | FULL TEXT  

Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World
Kamangar et al.
JCO 2006;24:2137-2150.
ABSTRACT | FULL TEXT  

Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk.
Kirsh et al.
JNCI J Natl Cancer Inst 2006;98:245-254.
ABSTRACT | FULL TEXT  

Dual Association of {beta}-Carotene With Risk of Tobacco-Related Cancers in a Cohort of French Women
Touvier et al.
JNCI J Natl Cancer Inst 2005;97:1338-1344.
ABSTRACT | FULL TEXT  

Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women's Health Study: A Randomized Controlled Trial
Lee et al.
JAMA 2005;294:56-65.
ABSTRACT | FULL TEXT  

Low-Dose Aspirin and Vitamin E: Challenges and Opportunities in Cancer Prevention
Jacobs and Thun
JAMA 2005;294:105-106.
FULL TEXT  

Advances in the Biology of Lung Cancer Chemoprevention
Hirsch and Lippman
JCO 2005;23:3186-3197.
ABSTRACT | FULL TEXT  

A Randomized Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer Patients
Bairati et al.
JNCI J Natl Cancer Inst 2005;97:481-488.
ABSTRACT | FULL TEXT  

Nutritional Interventions in Cancer Prevention
Taylor and Greenwald
JCO 2005;23:333-345.
ABSTRACT | FULL TEXT  

Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality
Miller et al.
ANN INTERN MED 2005;142:37-46.
ABSTRACT | FULL TEXT  

Antioxidant Vitamin Supplementation Reduces Benzo(a)pyrene-DNA Adducts and Potential Cancer Risk in Female Smokers
Mooney et al.
Cancer Epidemiol. Biomarkers Prev. 2005;14:237-242.
ABSTRACT | FULL TEXT  

Dietary Antioxidants and Human Cancer
Borek
Integr Cancer Ther 2004;3:333-341.
ABSTRACT  

The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping {beta}-Carotene and Retinol Supplements
Goodman et al.
JNCI J Natl Cancer Inst 2004;96:1743-1750.
ABSTRACT | FULL TEXT  

The Effects of Long-Term Vitamin E Treatment on Gene Expression and Oxidative Stress Damage in the Aging Brown Norway Rat Epididymis
Jervis and Robaire
Biol. Reprod. 2004;71:1088-1095.
ABSTRACT | FULL TEXT  

Hormones and Supplements: Do They Work?: Micronutrient Supplementation in Later Life: Limited Evidence for Benefit
Dangour et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2004;59:B659-B673.
ABSTRACT | FULL TEXT  

Consequences of Diabetes: Cardiovascular disease
Bloomgarden
Diabetes Care 2004;27:1825-1831.
FULL TEXT  

Frontiers in Cancer Prevention Research
Sabichi et al.
Cancer Res. 2003;63:5649-5655.
FULL TEXT