The combination of effects on lung cancer of cigarette smoking and exposure in quebec chrysotile miners and millers

Our plain-English summary of The combination of effects on lung cancer of cigarette smoking and exposure in quebec chrysotile miners and millers, by F.D. Liddell, B.G. Armstrong (The Annals of Occupational Hygiene, 2002).

The study

• Authors: F.D. Liddell, B.G. Armstrong
• Journal: The Annals of Occupational Hygiene
• Published: 2002;46(1):5-13
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although it is well known that both cigarette smoke and microscopic airborne asbestos fibres can cause lung cancer, evidence as to how these two agents combine is nebulous. Many workers have believed in the multiplicative theory, whereby asbestos increases the risk in proportion to the risk from other causes. However, evidence against this theory is mounting: a recent review concluded that the multiplicative hypothesis was untenable, and that the relative risk of lung cancer from asbestos exposure was about twice as high in non-smokers as in smokers, a finding largely independent of type of asbestos fibre. The criteria for entry to the current study were met by 7279 men in the 1891-1920 birth cohort of Quebec chrysotile miners and millers. The data consisted of date of birth, place of employment, smoking habit, asbestos exposure accumulated to age 55 and, for those 5527 who died between 1950 and June 1992, date and cause of death; 533 of the deaths were from lung cancer. For the principal analyses, ex-smokers were excluded from the study cohort, which comprised 5888 men, of whom 473 died of lung cancer. The conventional form of analysis is simply of the double dichotomy: non-smokers of cigarettes, 'unexposed' and exposed; all others, 'unexposed' and exposed. The respective standardized lung cancer mortality ratios (SMRs) were 0.29 and 0.62; and 1.37 and 1.72. Thus, the differences in relative risk, due to exposure, were closely similar, 0.33 and 0.35. On the other hand, the effects of asbestos measured by the corresponding ratios, 2.12 and 1.25, did differ, being 1.7 times as high in non-smokers as in others. The principal analysis was much more penetrating: the method was to fit models to a 'disaggregated' 6 x 10 array, by smoking habit (excluding ex-smokers) and asbestos exposure, of lung cancer SMRs. Both linear and log-linear models were fitted: the former included the additive and linear-multiplicative; the latter embraced the more conventional multiplicative form. The additive model fitted much the best. The fit of each multiplicative model was improved by the introduction of an interaction term that implied a less than multiplicative relationship. Thus smoking and exposure to chrysotile appear to have acted independently in causing lung cancer, with 10 cigarettes a day having an effect roughly equivalent to exposure amounting to 700 million particles per cubic foot x years. The refutation of the multiplicative hypothesis in these data reinforces its inapplicability in general; but the additive hypothesis is not generally applicable either. Indeed, there seems to be no good reason to believe that interactions conform to any simple theory. The implications are important.

In plain English

This study examined how cigarette smoking and exposure to chrysotile asbestos combined in their effect on lung cancer deaths among Quebec chrysotile miners and millers born between 1891 and 1920. Of 7279 eligible men, 5527 died between 1950 and May 1992, 533 of them from lung cancer. Most analyses left out ex-smokers, which left 5888 men and 473 lung cancer deaths. Exposure was the dust a man had accumulated by age 55, measured in million particles per cubic foot times years (mpcf.y). In a simple two-way split at 30 mpcf.y, lung cancer death ratios compared with Quebec men were 0.29 for less-exposed non-smokers and 0.62 for more-exposed non-smokers. For all others they were 1.37 and 1.72. The main analysis used six smoking groups and ten exposure groups. In it, a model in which the two effects simply add together fitted best, and multiplicative models fitted worse. In that model, 10 cigarettes a day added about as much as more than 700 mpcf.y. The authors concluded the effects were independent, or very nearly so. They noted that some non-smokers may have smoked pipes or cigars.

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 mortality study of a birth cohort, analysed by Poisson regression modelling of standardized lung cancer mortality ratios (SMRs)
• Who was studied: 7279 men in the 1891–1920 birth cohort of Quebec chrysotile miners and millers. 5527 of them had died (533 from lung cancer) between 1950 and 31 May 1992. The main analyses excluded 1391 ex-smokers, leaving 5888 men with 473 lung cancer deaths.
• Exposure: Chrysotile asbestos exposure accumulated to age 55, in million particles per cubic foot × years (mpcf.y), divided into ten classes. Cigarette smoking was divided into non-smokers, ex-smokers and five classes of current smokers. The Thetford Mines complex was dustier and had more tremolite contamination.
• Main results:
  • In the simple double dichotomy split at 30 mpcf.y, lung cancer SMRs were 0.29 (under 30 mpcf.y) and 0.62 (30 mpcf.y or more) in non-smokers of cigarettes. In all others they were 1.37 and 1.72.
  • In this simple split, the relative asbestos effect was 1.69 (95% confidence interval 0.87 to 3.28), so the multiplicative hypothesis could not be rejected on this evidence alone. The synergy index was 1.01 (95% confidence interval 0.73 to 1.41), close to the value for additivity but with a wide confidence interval.
  • In the main analysis of the 6 by 10 array (all 5888 men in the study cohort), the simple additive model fitted best. Its deviance was 62.2 on 57 df. The linear-multiplicative model had 66.3, and the log-linear multiplicative model had 79.2.
  • None of the log-linear (multiplicative-type) models fitted as well as the linear models.
  • In the additive model, 10 cigarettes a day added 0.727 to the SMR and 100 mpcf.y added 0.102. A non-smoker would need more than 700 mpcf.y to match the added effect of 10 cigarettes a day.
  • In a subsidiary analysis of all 7279 men, the risk parameter for ex-smokers fell between those for non-smokers and the lightest smokers.
• The authors' conclusion: The authors concluded that the multiplicative hypothesis could be discarded for these data. They found strong evidence that the effects of smoking and chrysotile exposure combined additively, meaning independently or very nearly so. They also noted that additivity is not a universal alternative.
• Limitations the authors state:
  • Some men classed as non-smokers of cigarettes may have smoked pipes or cigars, so the smoking-to-exposure equivalence may be slightly inflated.
  • Splitting the data by place of employment and birth decade led to considerable statistical instability.
  • The equivalence between cigarettes and exposure is a ratio of estimated parameters and has low accuracy.
  • Risk estimates for ex-smokers are averages that ignore how much and for how long they smoked, and when they quit.
  • 891 smoking questionnaires, mostly from proxies, were unreliable and had to be excluded.
  • The risk estimates in Table 8 are not intended for setting control limits.

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, Quebec Chrysotile, Relative Risk, Asbestos Exposure, Habit, Chrysotile, Million Particles per Cubic Foot (mppcf).

Related studies

• The 1891-1920 birth cohort of Quebec chrysotile miners and millers: development from 1904 and mortality to 1992 — F.D. Liddell, A.D. McDonald, et al. (1997)
• The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88 — J.C. McDonald, F.D. Liddell, et al. (1993)
• Asbestos exposure, cigarette smoking, and airflow limitation in long-term Canadian chrysotile miners and millers — R. Bégin, R. Boileau, et al. (1987)
• Long-term mortality experience of chrysotile miners and millers in Thetford Mines, Quebec — W.J. Nicholson, I.J. Selikoff, et al. (1979)
• Follow-up respiratory measurements in Quebec chrysotile asbestos miners and millers — M.R. Becklake, D. Thomas, et al. (1982)
• Exposure to chrysotile mining dust and digestive cancer mortality in a Chinese miner/miller cohort — S. Lin, X. Wang, et al. (2014)

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