Chemoprevention or antichemoprevention? A salutary warning From the beta-carotene experience

Our plain-English summary of Chemoprevention or antichemoprevention? A salutary warning From the beta-carotene experience, by M. Paolini, S.Z. Abdel-Rahman, G. Cantelli-Forti, et al (Journal of the National Cancer Institute, 2001).

The study

• Authors: M. Paolini, S.Z. Abdel-Rahman, G. Cantelli-Forti, M.S. Legator
• Journal: Journal of the National Cancer Institute
• Published: 2001;93(14):1110-1
• Type of article: Comment, Letter
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, Paolini and colleagues noted that the ATBC and CARET chemoprevention trials had shown that beta-carotene, alone or combined with vitamins A or E, could increase lung cancer incidence and mortality in heavy smokers and asbestos workers. They summarised their own earlier laboratory findings. In an animal model, beta-carotene supplementation greatly increased lung production of cytochrome P450 (CYP) carcinogen-bioactivating enzymes, and this was associated with oxidative stress. In the BALB/c 3T3 bioassay, which they reported correlates 70%–85% with in vivo carcinogenesis, beta-carotene markedly enhanced the conversion of 3-methylcholanthrene and benzo[a]pyrene to ultimate carcinogens. Blocking the CYP increase or the overproduction of reactive oxygen species removed these effects. The authors argued that genetic polymorphisms in bioactivating, detoxifying or DNA repair enzymes could confound trial results. They said mechanistic and toxicologic studies, and the genetic make-up of trial populations, should be considered before human trials. They also supported continued advice on high fruit and vegetable intake and on smoking cessation. In a published response, Omenn described oxidative metabolites of beta-carotene and a ferret study. In that study, a dose equivalent to 30 mg per day in humans caused proliferative changes and squamous metaplasia in the lung, while one fifth of that dose did not. He disputed the letter's pessimistic conclusion about chemoprevention.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This item is a letter to the editor, followed by a reply, and reports no new study data. The letter's authors noted that two lung cancer prevention trials, ATBC and CARET, had shown that beta-carotene, alone or combined with vitamin A or E, could increase lung cancer incidence and mortality in heavy smokers and asbestos workers. They summarized their own earlier laboratory work, published elsewhere. In an animal model, beta-carotene raised the lungs' production of enzymes that turn chemicals into active carcinogens. In a cell test, it enhanced the conversion of cancer-causing chemicals, including one found in cigarette smoke. They argued that the genetic make-up of trial participants should be considered before such trials. The authors concluded that it may be naive, and possibly dangerous, to base cancer chemoprevention on giving only one or a few chemicals. In a reply, Gilbert S. Omenn described a separate ferret study and called beta-carotene a potent human nongenotoxic carcinogen. The reply disagreed with the letter's final sentence, noting that many individual drugs are effective and safe. Neither piece gave separate figures for asbestos workers.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: letter to the editor (correspondence) with a reply from another author; no original study
• Exposure: beta-carotene supplements, as given in the ATBC and CARET trials (described from other publications), whose participants included heavy smokers and asbestos workers
• The authors' conclusion: The letter's authors concluded that it may be naive, and possibly dangerous, to base cancer chemoprevention on giving only one or a few chemicals. In the reply, Omenn called this final sentence possibly unwarranted.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Oxidative Stress, Carcinogenesis, Reactive Oxygen Species (ROS).

Related studies

• 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 — G.E. Goodman, M.D. Thornquist, et al. (2004)
• Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene — N.H. de Klerk, A.W. Musk, et al. (1998)
• Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial — G.S. Omenn, G.E. Goodman, et al. (1996)
• Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression — J. Kordiak, F. Bielec, et al. (2022)
• Chemoprevention of cancer: lessons to be learned from beta-carotene trials — H. Vainio (2000)
• The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort — P. Chuwers, S. Barnhart, et al. (1997)

Browse more research in Journal of the National Cancer Institute, or return to medical research.