Consensus on synergism between cigarette smoke and other environmental carcinogens in the causation of lung cancer

Our plain-English summary of Consensus on synergism between cigarette smoke and other environmental carcinogens in the causation of lung cancer, by A.E. Reif, T. Heeren (Advances in Cancer Research, 1999).

The study

• Authors: A.E. Reif, T. Heeren
• Journal: Advances in Cancer Research
• Published: 1999;76:161-86
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This review examined whether there was statistically verifiable evidence of synergism between cigarette smoking and other environmental carcinogens, mainly asbestos and radon, in causing lung cancer. The authors proposed using synergism as a new message in antismoking campaigns in developed countries. They defined synergism as a joint effect greater than the sum of the separate effects, and argued that dose-response curves must be linear for a simple test to be valid. They fitted weighted linear regression models to published standardized mortality ratio data and found linear fits for cigarette smoking (Hammond, 1966; R-square 0.98), asbestos (Dement et al., 1982, R-square 0.97; McDonald et al., 1983, R-square 0.98) and radon in uranium miners (R-square 0.91 and 0.95). Applying a modified z-test to data from Hammond et al. (1979), lung cancer occurred in 276/6841 asbestos workers who smoked, 303/37,000 smokers, 4/891 nonsmoking asbestos workers and 28/37,000 controls. This synergism was significant (P < 0.01), and risk was multiplicative. For radon, residential data showed borderline significance (0.05 < P < 0.10) and uranium miner data were significant (P < 0.01). Data on smoking and alcohol did not meet the authors' criteria. A simple model suggested that synergism seen with short follow-up might become additive with long follow-up. The authors concluded that there is a consensus that smoking interacts synergistically with asbestos or radon in causing lung cancer.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a review that re-analysed published lung cancer data. The authors set out to test whether cigarette smoke acts synergistically, meaning more than additively, with asbestos, radon and alcohol. They first fitted straight-line models to published dose-response data and reported close fits: an R-square of 0.98 for cigarettes per day, 0.97 and 0.98 for cumulative asbestos exposure in two studies of males, and 0.91 and 0.95 for radon in two studies of uranium miners. They then applied their test to data from Hammond and colleagues (1979). Lung cancer occurred in 276/6841 people exposed to both smoking and asbestos, 303/37,000 smokers, 4/891 nonsmoking asbestos workers and 28/37,000 controls. The authors found this synergism significant (P less than 0.01). They noted that this follow-up did not extend to the end of all subjects' lives. They also used a simple model to show that a long follow-up may not show synergism. Data on smoking and alcohol did not meet their criteria. The authors concluded that a consensus exists that lung cancer caused by cigarette smoke interacting with asbestos or radon is synergistic.

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: Review with re-analysis of previously published data; no new subjects were studied
• Who was studied: Published data from other studies: an American Cancer Society study of about a million men and women (Hammond 1966); asbestos-exposed males (Dement et al. 1982; McDonald et al. 1983); uranium miners (Muller et al. 1985; Howe et al. 1986; Lundin et al. 1969); smokers, asbestos workers and controls (Hammond et al. 1979); residential radon cases and controls in Sweden (Pershagen et al. 1994)
• Exposure: Inhaled cigarette smoke, radon gas and asbestos fibers, alone and in combination with smoking. Alcohol was also considered for cancers of the mouth, pharynx, larynx and esophagus. Fiber types in the analysed asbestos studies are not stated.
• Main results:
  • For cigarettes per day and lung cancer mortality ratios (American Cancer Society data), a straight-line model fitted with an R-square of 0.98
  • For cumulative asbestos exposure and lung cancer mortality ratios, straight-line models fitted both data sets well: an R-square of 0.97 for the Dement et al. (1982) data and 0.98 for the McDonald et al. (1983) data
  • For cumulative radon exposure in uranium miners, straight-line models gave an R-square of 0.91 for the Ontario data and 0.95 for the Eldorado data
  • In the Hammond et al. (1979) data, lung cancer incidence was 276/6841 in the group exposed to both smoking and asbestos, 303/37,000 in cigarette smokers, 4/891 in asbestos workers who were nonsmokers, and 28/37,000 in controls
  • Using these Hammond et al. data, the authors found synergism between smoking and asbestos that was statistically significant (P less than 0.01) and, in their classification, consistent with strict synergism
  • For smoking and residential radon (Pershagen et al. 1994 data), synergism was of borderline statistical significance (P between 0.05 and 0.10)
  • For smoking and alcohol, the available data did not meet the authors' criteria for statistically showing synergism
  • A simplified two-step model illustrated that a short follow-up may show synergism while a long follow-up may not
• The authors' conclusion: The authors concluded that a consensus exists that lung cancer caused by cigarette smoke interacting with either asbestos or radon is synergistic
• Limitations the authors state:
  • The smoking-asbestos data did not cover the full life span of all subjects
  • Because the data were standardized mortality ratios, the analysis assumed that age-specific dose-response curves are parallel
  • None of the studies used had enough data on the timing of the two exposures to allow a time-dependent test
  • The residential radon data were limited
  • The follow-up model was a simplified two-step model, not a more realistic multistep model

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: Causation, Lung Cancer, Dose-response relationship, standardized mortality ratio (SMR).

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