Low-dose exposure to asbestos and lung cancer: dose-response relations and interaction with smoking in a population-based case-referent study in Stockholm, Sweden

Our plain-English summary of Low-dose exposure to asbestos and lung cancer: dose-response relations and interaction with smoking in a population-based case-referent study in Stockholm, Sweden, by P. Gustavsson, F. Nyberg, G. Pershagen, et al (American Journal of Epidemiology, 2002).

The study

• Authors: P. Gustavsson, F. Nyberg, G. Pershagen, P. Schéele, R. Jakobsson, N. Plato
• Journal: American Journal of Epidemiology
• Published: 2002;155(11):1016-22
• Cited by: 76 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This population-based case-referent study investigated the lung cancer risk associated with occupational exposure to asbestos, focusing on dose-response relations and the interaction with tobacco smoking. Incident cases of lung cancer among males aged 40-75 years in Stockholm County, Sweden, were identified from 1985 to 1990. Referents were selected randomly within strata (age, inclusion year) of the study base. Questionnaires administered to subjects or their next of kin gave information on occupations, tobacco smoking habits, and residences. Response rates of 87% and 85% resulted in 1,038 cases and 2,359 referents, respectively. Occupational exposures were assessed by an industrial hygienist. Lung cancer risk increased almost linearly with cumulative dose of asbestos. The risk at a cumulative dose of 4 fiber-years was 1.90 (95% confidence interval (CI): 1.32, 2.74), higher than that predicted by downward linear extrapolation from highly exposed occupational cohorts. The relative risk (exp(beta)) for a transformed dose variable ln(fiber-years + 1) was 1.494 (95% CI: 1.193, 1.871) per unit of exposure. The joint effect of asbestos and smoking was estimated to be 1.15 (95% CI: 0.77, 1.72) times that predicted from the sum of their individual effects and 0.31 (95% CI: 0.11, 0.86) times that predicted from their product, indicating a joint effect between additivity and multiplicativity.

In plain English

This population-based case-referent study compared 1,038 men aged 40 to 75 in Stockholm County, Sweden, diagnosed with lung cancer from 1985 to 1990, with 2,359 randomly selected referents. Questionnaires answered by the men or their next of kin covered jobs and smoking. An industrial hygienist, blinded to who had cancer, used these to estimate each man's cumulative occupational asbestos dose in fiber-years. Doses were low, at most 20.4 fiber-years. Lung cancer risk rose almost linearly with dose. At 4 fiber-years the relative risk was 1.90 (95% CI 1.32 to 2.74). The risk per unit of dose was higher in never smokers than in current smokers. Comparing current smokers with lifelong nonsmokers, and men with at least 1 fiber-year with unexposed men, the authors found a combined risk lower than the product of the separate risks (interaction term 0.31, 95% CI 0.11 to 0.86) and close to their sum (synergy index 1.15, 95% CI 0.77 to 1.72). The authors concluded that there was a clear excess lung cancer risk at low doses, which linear extrapolation from high exposure levels underestimates.

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: Population-based case-referent (case-control) study using postal questionnaires sent to subjects or, for deceased subjects, their next of kin
• Who was studied: Men aged 40 to 75 resident in Stockholm County, Sweden, 1985 to 1990: 1,038 lung cancer cases and 2,359 referents (response rates 87% for cases and 85% for referents)
• Exposure: Occupational asbestos exposure, expressed as cumulative dose in fiber-years (intensity times probability times duration, summed over work periods). It was assessed by an industrial hygienist blinded to case or referent status. The authors note that chrysotile was by far the most common asbestos type used in Stockholm. Smoking was studied as a co-exposure.
• Main results:
  • 20.0% of cases and 14.4% of referents had ever been exposed to asbestos for at least 1 year
  • Cumulative asbestos doses were low, ranging from zero (or environmental background levels) to a maximum of 20.4 fiber-years
  • Lung cancer risk increased almost linearly with cumulative asbestos dose. The relative risk at 4 fiber-years was 1.90 (95% CI 1.32, 2.74), across all men.
  • The relative risk per unit of the transformed dose variable ln(fiber-years + 1) was 1.494 (95% CI 1.193, 1.871), across all men
  • For never smokers, the relative risk per unit of ln(fiber-years + 1) was 2.848 (95% CI 1.486, 5.458), corresponding to 5.38 at 4 fiber-years
  • For current smokers, the relative risk per unit of ln(fiber-years + 1) was 1.345 (95% CI 1.024, 1.767), corresponding to a relative risk of 1.55 at 4 fiber-years
  • In the dichotomized analysis comparing asbestos exposure of 1 fiber-year or more with none, and current smokers with lifelong nonsmokers (former smokers and men exposed below 1 fiber-year excluded), the interaction term in the multiplicative model was 0.31 (95% CI 0.11, 0.86), indicating a less than multiplicative joint effect
  • In the same analysis, the synergy index was 1.15 (95% CI 0.77, 1.72), which the authors described as a joint effect close to additivity
  • A model using continuous variables for asbestos and smoking gave an interaction term of 0.85 (95% CI 0.73, 0.99), again indicating a submultiplicative joint effect
  • For men with 2.5 fiber-years or more who also smoked more than 20 cigarettes a day, the observed relative risk was 80.6, considerably lower than the risk predicted by a multiplicative model
  • For asbestos exposure of 2.5 fiber-years or more versus none, the relative risk was 1.84 (95% CI 1.00, 3.38) with population referents and 2.00 (95% CI 1.08, 3.67) with mortality-matched referents
• The authors' conclusion: The authors concluded that there was a clear excess risk of lung cancer at low-dose levels and that linear extrapolation from high exposure levels underestimates the risk at low doses. They also found the joint effect of asbestos and smoking to be submultiplicative but slightly more than additive, and said further studies seem warranted on the shape of the low-dose dose-response curve.
• Limitations the authors state:
  • Occupational histories for cases were often obtained from next of kin because of short survival, which may have led to some underestimation of asbestos exposure
  • Systematic and uniform under- or overestimation of exposure cannot be ruled out, since the assessments relied on external exposure data
  • The study gives no information on risk at higher cumulative doses and has reasonable precision only for doses up to about 5 fiber-years
  • Only six nonsmoking cases had 2.5 fiber-years or more. Recoding one of them as a former smoker changed the interaction term to 0.37 (95% CI 0.13, 1.09), which was not formally statistically significant.
  • The dose-response did not increase monotonically in all smoking strata, probably because of low numbers, as shown by wide confidence intervals

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, Dose-response relationship, Occupational Exposure, Habit, Cumulative Dose, Fiber Year, confidence interval, Relative Risk.

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• Urban air pollution and lung cancer in Stockholm — F. Nyberg, P. Gustavsson, et al. (2000)
• Calculation of fractions of lung cancer incidence attributable to occupational exposure to asbestos and combustion products in Stockholm, Sweden — P. Gustavsson, A. Ahlbom, et al. (2003)
• A case-referent study of cancer mortality among sulfate mill workers in Sweden — E. Andersson, S. Hagberg, et al. (2001)
• Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study — Y. Iwatsubo, J.C. Pairon, et al. (1998)
• Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions — M. El Zoghbi, P. Salameh, et al. (2017)

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