Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET)

Our plain-English summary of Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET), by C.A. Brodkin, J. McCullough, B. Stover, et al (American Journal of Industrial Medicine, 1997).

The study

• Authors: C.A. Brodkin, J. McCullough, B. Stover, J. Balmes, S. Hammar, G.S. Omenn, H. Checkoway, S. Barnhart
• Journal: American Journal of Industrial Medicine
• Published: 1997;32(6):582-91
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

In plain English

This study examined lung cancers in CARET, a vitamin trial to prevent lung cancer. The authors compared 78 male asbestos-exposed workers with 214 heavy smokers without occupational asbestos exposure. They asked whether lower-lobe tumors and adenocarcinoma, sometimes used to attribute lung cancer to asbestos, were more common with asbestos. Among cases with an identifiable lobe (73 asbestos-exposed, 167 smokers), most tumors arose in the upper or right middle lobe: 67% and 80% respectively. Before adjustment, lower-lobe tumors were more likely in the asbestos group (odds ratio 1.92, 95% CI 1.03 to 3.55). Adjusted for smoking, age, gender and vitamin treatment, it was 1.41 (95% CI 0.69 to 2.91). Adenocarcinoma made up 24 of 74 classifiable asbestos-group tumors (32%) and 62 of 204 smokers' tumors (30%). Among asbestos-exposed workers with lung cancer, enrollment X-ray fibrosis was linked to lower odds that the tumor was adenocarcinoma (odds ratio 0.19, 95% CI 0.06 to 0.62). No lung cancers occurred among 132 asbestos-exposed pilot participants who never smoked. The authors concluded that neither lobe of origin nor tumor histology can convincingly establish asbestos causation.

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: Prospective comparison of lung cancer cases arising within a multicenter randomized lung cancer chemoprevention trial (CARET). The trial tested beta-carotene and retinyl palmitate (vitamin A) against placebo.
• Who was studied: Participants came from 4,060 asbestos-exposed workers and 14,254 heavy smokers enrolled in CARET at six study centers. Accrual began in 1985, and the vitamin intervention was halted in January 1996, after a mean follow-up of 4.0 years.

Of 304 lung cancer cases with completed review, 12 with multiple cancer sites were excluded. That left 292 cases: 78 asbestos-exposed workers and 214 heavy smokers.

• Lobe-of-origin analyses used 240 cases (73 asbestos-exposed, 167 smokers).
• Histology analyses used 278 cases (74 asbestos-exposed, 204 smokers).

The asbestos-exposed group was all male, aged 45 to 69 at enrollment. The smoking group included men and women aged 50 to 69 with at least 20 pack-years of smoking.

• Exposure: Occupational asbestos exposure, defined as more than 5 years of employment in a high-risk trade or a chest radiograph showing asbestos-related effects. No fiber type was specified.

Among the 78 asbestos-exposed cases:

• mean total exposure was 30 years, including 22 years in a high-risk trade;
• mean time from first exposure to enrollment was 40 years;
• on baseline radiographs, 10 (13%) were normal, 19 (24%) had pleural changes only, and 49 (63%) had small opacities of ILO 1/0 or higher.

The comparison group was heavy smokers with no occupationally related asbestos exposure.

• Main results:
  • Among cases with an identifiable lobe, most tumors in both groups were non-lower-lobe tumors:
• 49 of 73 (67%) in asbestos-exposed workers;
• 133 of 167 (80%) in heavy smokers.

The article labels these "upper lobe" tumors, but right middle lobe tumors (7 asbestos-exposed, 12 nonexposed) were counted with them.

• Before adjustment, the asbestos-exposed group showed a statistically significant tendency toward lower-lobe tumors compared with heavy smokers (OR 1.92; 95% CI 1.03 to 3.55).
• In logistic regression adjusting for smoking status, pack-years, gender, age and vitamin arm, asbestos exposure compared with heavy smoking gave two results:
• for lower-lobe origin, OR 1.41 (95% CI 0.69 to 2.91), which the authors called a weak association;
• for adenocarcinoma, OR 0.78 (95% CI 0.40 to 1.55), which the authors described as no significant association.
  • Among cases available for histologic analysis, adenocarcinoma was the most frequent cell type in both groups: 24 of 74 (32%) in asbestos-exposed workers and 62 of 204 (30%) in heavy smokers.

Squamous cell carcinoma made up 32% in the asbestos group and 20% in smokers. Large and small cell tumors together made up 31% in the asbestos group and 45% in smokers.

• Within the asbestos-exposed group, radiographic fibrosis at baseline (ILO profusion 1/0 or higher) was not significantly associated with lower-lobe origin (adjusted OR 1.09; 95% CI 0.37 to 3.20).

Lower-lobe tumors made up 31% of cancers in workers with ILO rating below 1/0, 33% in those rated 1/0 to 1/2, and 37% in those rated 2/1 or higher.

• Among the 74 asbestos-exposed workers with lung cancer, radiographic fibrosis was inversely associated with the tumor being adenocarcinoma rather than another cell type (adjusted OR 0.19; 95% CI 0.06 to 0.62). Adenocarcinoma made up:
• 50% (14/28) of cancers with ILO rating below 1/0;
• 24% (9/38) with rating 1/0 to 1/2;
• 13% (1/8) with severe changes.
  • No lung cancers were observed among the 132 asbestos-exposed pilot participants who had never smoked.
  • Vitamin intervention arm was not associated with lobe of origin or histologic cell type.
• The authors' conclusion: The authors concluded that lung cancers arose more often in the upper lobes in both asbestos-exposed and non-exposed participants, without a predominant cell type. In their view, neither lobe of origin nor tumor histology can be used convincingly to determine that asbestos caused a lung cancer.
• Limitations the authors state:
  • The trial vitamins might have affected smokers and asbestos-exposed workers differently and confounded the findings. The authors judged this unlikely because no significant intervention effect was found.
  • No never-smokers in the asbestos group developed lung cancer, so the effect of asbestos could not be strictly assessed apart from smoking.
  • There were no specific quantitative measurements of past asbestos exposure, such as lung fiber burden or airborne monitoring data. This prevented a more specific dose-response assessment.
  • Differences in age and gender between the groups might have confounded the results. The authors judged this unlikely based on their analyses.
  • Few participants had radiographic fibrosis, especially in the higher ILO categories. This limits inferences about the inverse association between fibrosis and adenocarcinoma.
  • Only baseline radiographs were used, so fibrosis at the time each tumor developed could not be determined.

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, Asbestos Exposure, Adenocarcinoma, Fibrosis.

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)
• Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial — M.D. Thornquist, N. Urban, et al. (1993)
• 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)
• Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET) — B. Cartmel, J. Dziura, et al. (2005)
• Predictors of lung cancer among asbestos-exposed men in the {beta}-carotene and retinol efficacy trial — M.R. Cullen, M.J. Barnett, et al. (2005)

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