Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial

Our plain-English summary of Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial, by M.R. Cullen, M.J. Barnett, J.R. Balmes, et al (American Journal of Epidemiology, 2005).

The study

• Authors: M.R. Cullen, M.J. Barnett, J.R. Balmes, B. Cartmel, C.A. Redlich, C.A. Brodkin, S. Barnhart, L. Rosenstock, G.E. Goodman, S.P. Hammar, M.D. Thornquist, G.S. Omenn
• Journal: American Journal of Epidemiology
• Published: 2005;161(3):260-70
• Type of article: Randomized trial
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

In plain English

This study analyzed CARET, a randomized lung cancer prevention trial of beta-carotene and vitamin A. It followed 3,897 asbestos-exposed US men, all current or former smokers, for 9 to 17 years; 241 developed lung cancer. Among 1,839 exposed men also meeting the trial's heavy-smoker criteria, those with pleural changes had a relative risk of 1.44 (95% CI 1.15 to 1.79) versus unexposed heavy smokers. In this subgroup, risk rose with X-ray asbestosis grade, reaching 4.42 (95% CI 1.83 to 10.69; 5 cases in 16 men) in the highest category, ILO 3/2 to 3/+. Across all exposed men, the rise with X-ray grade was steep with the vitamins but small and non-significant with placebo. Among 2,089 trade workers with normal lung tissue on X-ray, over 40 years in a high-risk trade carried a relative risk of 5.17 (95% CI 1.61 to 16.6) versus under 10 years. Here, pleural changes roughly doubled risk, and poorer lung function predicted cancer. The authors concluded that risk rises with exposure duration even without clinical asbestosis. They could not say whether asbestos itself or asbestosis invisible on X-ray explains this.

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: Observational analysis of the asbestos-exposed group in a randomized, double-blind, placebo-controlled lung cancer chemoprevention trial (CARET), followed prospectively and analyzed with stratified Cox proportional hazards models
• Who was studied: 3,897 asbestos-exposed US men analyzed out of 4,060 enrolled. They were recruited at five centers (Seattle, Baltimore, Portland, New Haven, San Francisco), in a 1985–1988 pilot phase and in 1989–1993. All were current or former smokers aged 45 to 74, and follow-up ran through October 31, 2002. The comparison group was 7,924 male heavy smokers in the same trial who were not asbestos-exposed.
• Exposure: Occupational asbestos exposure, documented in one of two ways. The first was at least 5 years in a designated high-risk trade (insulation, sheet metal work, plumbing, plasterboard application, shipfitting, ship electrical work, boilermaking, ship scaling), starting at least 15 years earlier. The second was occupational exposure plus asbestos-related changes on X-ray. Years in a high-risk trade served as a stand-in for dose. Participants were randomized to beta-carotene (30 mg) plus retinyl palmitate (25,000 IU) daily, or placebo.
• Main results:
  • In the whole asbestos-exposed cohort there were 241 lung cancers among 3,897 men. This was an incidence rate of 5.9 per 1,000 person-years (95% CI 5.2, 6.7).
  • Asbestos-exposed men who also met the heavy-smoker criteria (1,839 men, 165 cases) had a higher lung cancer rate than the heavy smokers without asbestos exposure: relative risk 1.24 (95% CI 1.04, 1.47).
  • In the same smoker-eligible subgroup, compared with heavy smokers, men with pleural abnormalities (94 cases among 886) had a relative risk of 1.44 (95% CI 1.15, 1.79). Men without pleural abnormalities had a relative risk of 1.05 (95% CI 0.82, 1.34), which was not significant.
  • In the smoker-eligible subgroup compared with heavy smokers, risk rose with the X-ray grade of asbestosis. ILO profusion 1/0 to 1/2 had a relative risk of 1.42 (95% CI 1.12, 1.79). The highest major category, 3/2 to 3/+, had 5 cases among 16 men and a relative risk of 4.42 (95% CI 1.83, 10.69).
  • In the whole asbestos cohort, the vitamins and asbestosis grade appeared to interact. Among men on active vitamins, grade 3/2 to 3/+ had a relative risk of 12.45 (95% CI 4.47, 34.6) versus 0/– or 0/0. Among men on placebo, the same comparison gave 1.92 (95% CI 0.25, 14.9), with a non-significant trend.
  • Among 2,089 work-history-eligible men with normal lung tissue on X-ray (ILO below 1/0), risk rose with years in a high-risk trade. Men with more than 40 years (12 cases among 86 men) had a relative risk of 5.17 (95% CI 1.61, 16.6), compared with under 10 years (6 cases among 272). The p for trend was 0.007, and the vitamins did not appear to modify this.
  • In the same group with normal lung tissue on X-ray, pleural abnormality was associated with a relative risk of 1.91 (95% CI 1.25, 2.92).
  • In the same group, lower baseline lung function predicted lung cancer. An FEV1:FVC ratio below 60 percent had a relative risk of 9.87 (95% CI 3.23, 30.1) versus 80 percent or more. FEV1 below 60 percent of predicted had a relative risk of 5.17 (95% CI 2.81, 9.50).
• The authors' conclusion: The authors concluded that, among current and former smokers exposed to asbestos at work, lung cancer risk increases with exposure duration even without clinical evidence of asbestosis. They also concluded that men with pleural plaques and pre-existing obstructive lung disease are at higher risk. In their view, neither residual confounding by smoking nor hidden asbestosis appeared to explain the findings.
• Limitations the authors state:
  • The authors could not determine whether the excess risk in men without X-ray fibrosis is a direct effect of asbestos or comes from asbestosis not visible on X-ray.
  • The authors described the synergy between asbestosis and the vitamins as new and not yet confirmed.
  • Almost 80 percent of participants were exposed in shipbuilding or construction trades. Manufacturing and other settings were underrepresented.
  • Exposure could only be measured crudely, as years in a high-risk trade.
  • Participants were not classified by exposure dose, fiber type or fiber size.
  • Chest X-rays were read by separate readers at each center rather than by a single panel.
  • Participants were trial volunteers, who may differ from comparable men in the general population.
  • The results cannot be applied to women, men with lesser asbestos exposure, or lifelong nonsmokers.
  • The authors could not entirely exclude effects of other unmeasured workplace carcinogens, such as welding fumes, diesel exhaust or silica.

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Parenchyma, Chest X-Ray, Pleural Plaques, Confounding, Carcinogenic.

Related studies

• 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)
• Evidence for excess colorectal cancer incidence among asbestos-exposed men in the Beta-Carotene and Retinol Efficacy Trial — O.A. Aliyu, M.R. Cullen, et al. (2005)
• 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)
• CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers — G.S. Omenn, G. Goodman, et al. (1991)
• Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers — G.S. Omenn, G. Goodman, et al. (1992)
• Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET) — C.A. Brodkin, J. McCullough, et al. (1997)

Browse more research in American Journal of Epidemiology, or return to medical research.