Lung cancer in chrysotile asbestos workers: analyses based on the two-stage clonal expansion model

Our plain-English summary of Lung cancer in chrysotile asbestos workers: analyses based on the two-stage clonal expansion model, by D.B. Richardson (Cancer Causes & Control, 2009).

The study

• Author: D.B. Richardson
• Journal: Cancer Causes & Control
• Published: 2009;20(6):917-23
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To evaluate the magnitude and temporal pattern of lung cancer risk following exposure to chrysotile asbestos.

Methods: I analyzed data on lung cancer mortality in a cohort of asbestos textile workers who were exposed to almost pure chrysotile. Employment history and industrial hygiene data were used to derive asbestos exposure estimates. These data were analyzed within the framework of the two-stage clonal expansion (TSCE) model and the Cox proportional hazards model.

Results: Under the TSCE model, the association between chrysotile asbestos and lung cancer mortality was primarily due to an exposure-induced increase in the proliferation of initiated cells. In a setting of protracted exposure to chrysotile asbestos, this model implies that the estimated hazard ratio was at its maximum between ages 40 and 65 years. Cox regression analyses support these conclusions; the estimated excess relative risk per fiber-year/ml was 0.053 (95% CI: 0.023, 0.124) at ages <65 years, while there was minimal evidence of association at older attained ages.

Conclusions: The TSCE model fits these data well, accommodating the observed departure from the proportional hazards assumption. These analyses suggest that the effect of chrysotile asbestos exposure on lung cancer risk varies with attained age.

In plain English

This study re-analyzed lung cancer deaths among 1,256 white male workers at a South Carolina chrysotile asbestos textile plant. The men had worked in production at least a month between 1940 and 1965; by 2001, 116 had died of lung cancer. Each man's cumulative exposure, in fiber-years per milliliter, was estimated from job histories and job exposure rates. The author used a cancer-development model (two-stage clonal expansion) and Cox regression. The model fit best when asbestos was assumed to speed growth of pre-cancerous cells. About 26 of the 116 deaths were estimated to be excess cases associated with asbestos. With a 10-year lag, the excess relative risk per fiber-year/ml was 0.015 (95% CI 0.007 to 0.028) overall, 0.053 (95% CI 0.023 to 0.124) at ages under 65, and 0.003 (95% CI lower limit not determined, upper 0.012) at ages 65 or older, where there was little evidence of association. The author concluded that chrysotile's effect on lung cancer risk appeared to vary with attained age. The author called the lack of smoking information a clear limitation.

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: Cohort study of lung cancer mortality, analyzed with a two-stage clonal expansion (TSCE) model of carcinogenesis and with Cox proportional hazards regression
• Who was studied: 1,256 white male production workers at an asbestos textile plant in South Carolina, employed at least one month between January 1, 1940 and December 31, 1965, with vital status followed through December 31, 2001; 116 died of lung cancer
• Exposure: Chrysotile asbestos (received from Quebec, British Columbia, and Zimbabwe) in asbestos textile production. Cumulative exposure was given in fiber-years/ml, computed from length of employment in each job and the estimated exposure rate for that job, mainly with a 10-year lag.
• Main results:
  • In the TSCE model, the best fit came from a linear effect of asbestos on the proliferation rate of initiated (pre-malignant) cells
  • Comparing observed deaths with the number expected with no exposure effect, about 26 of the 116 lung cancer deaths were estimated to be excess cases associated with asbestos exposure
  • For a modeled person exposed at 5 or 2.5 fiber/ml from age 20 to 60, the predicted hazard ratio rose with attained age until about age 55 and then fell
  • In Cox regression with a 10-year lag, the excess relative risk per fiber-year/ml for lifetime cumulative exposure was 0.015 (95% CI 0.007, 0.028)
  • With a 10-year lag, the excess relative risk per fiber-year/ml was 0.053 (95% CI 0.023, 0.124) at attained ages under 65. At ages 65 or older it was 0.003 (95% CI lower limit not determined, upper 0.012). The test of difference gave LRT 14.0, p = 0.0001.
  • Under 5-year and 15-year lag assumptions, cumulative exposure was also positively associated with lung cancer mortality (ERR 0.015, 95% CI 0.007, 0.027 and ERR 0.015, 95% CI 0.006, 0.029)
• The authors' conclusion: The author concluded that the TSCE model fit the data well, and that the hazard ratio rose and then fell with attained age, reaching its maximum between ages 40 and 65
• Limitations the authors state:
  • No information on cigarette smoking
  • Validity depends partly on the accuracy of the asbestos exposure estimates
  • A good model fit does not by itself show that the theoretical disease model is valid

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, Chrysotile, Industrial Hygiene, Asbestos Exposure, Hazard Ratio, Relative Risk.

Related studies

• The two-stage clonal expansion model in occupational cancer epidemiology: results from three cohort studies — A. Zeka, R. Gore, et al. (2011)
• Follow-up study of chrysotile asbestos textile workers: cohort mortality and case-control analyses — J.M. Dement, D.P. Brown, et al. (1994)
• Increased lung cancer mortality among chrysotile asbestos textile workers is more strongly associated with exposure to long thin fibres — D. Loomis, J.M. Dement, et al. (2012)
• An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers — L. Stayner, E. Kuempel, et al. (2008)
• Mesothelioma mortality in asbestos workers: implications for models of carcinogenesis and risk assessment — J. Peto, H. Seidman, et al. (1982)
• Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers — F.H. Green, R. Harley, et al. (1997)

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