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Original Contribution
JAMA. 2003;290(4):476-485. doi: 10.1001/jama.290.4.476

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

A Postintervention Follow-up

  1. The ATBC Study Group
  1. 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.

Abstract

Context  In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, α-tocopherol supplementation decreased prostate cancer incidence, whereas β-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 α-tocopherol and β-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 α-tocopherol (50 mg), β-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 β-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving α-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 α-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for β-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for β-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 α-tocopherol and β-carotene disappeared during postintervention follow-up. The preventive effects of α-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid β-carotene supplementation.

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