The molecular epidemiology of asbestos and tobacco in lung cancer

Our plain-English summary of The molecular epidemiology of asbestos and tobacco in lung cancer, by H.H. Nelson, K.T. Kelsey (Oncogene, 2002).

The study

• Authors: H.H. Nelson, K.T. Kelsey
• Journal: Oncogene
• Published: 2002;21(48):7284-8
• Type of article: Review
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos is a well-known toxin and lung carcinogen. Epidemiologic studies have established tobacco smoke and asbestos exposures synergistically interact to enhance lung cancer risk. The biologic mechanism responsible for this interaction has been the subject of considerable debate. Studies have suggested that asbestos may act as a carcinogen by generating free radical and reactive oxygen species, by inducing tissue injury and subsequent cellular growth, via large-scale chromosome loss and by enhancing delivery of tobacco carcinogens to the respiratory epithelium. Recent molecular epidemiologic approaches further suggest that asbestos enhances the mutagenicity of tobacco carcinogens and that it acts, at least in part, independent of the tissue damage responsible for fibrosis.

In plain English

This was a review reporting no new data. The authors summarized research on how asbestos and tobacco smoke together raise lung cancer risk. They cited a 1968 study by Selikoff and colleagues of workers with significant exposure to both, in which asbestos alone was associated with about a fivefold increase in lung cancer risk, smoking alone about 10-fold, and both together about 50-fold above unexposed workers. The authors stressed that these risks depend on dose and time and that estimates varied considerably across studies. They described mechanisms proposed by other studies, including reactive oxygen species, tissue injury, chromosome loss, and fibers carrying tobacco carcinogens into lung cells. They reviewed tumor studies linking asbestos exposure to FHIT gene deletion and to tobacco-type k-ras and p53 mutations. Some k-ras mutations occurred in exposed people without fibrotic changes. The authors concluded that combined exposure appears to produce more tobacco-type mutations and that these changes may be independent of fibrosis. They noted limits: asbestos exposure is hard to estimate, and lung cancer in non-smoking asbestos-exposed people is becoming rarer in the United States.

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: Narrative review of published epidemiologic, laboratory and molecular epidemiologic studies; no original data
• Who was studied: No study population of its own; the article reviewed previously published studies of asbestos-exposed workers, lung tumors and laboratory systems
• Exposure: Asbestos (serpentine chrysotile and amphibole asbestos, notably amosite and crocidolite) and tobacco smoke, alone and combined
• Main results:
  • Citing Selikoff et al. (1968), in workers with significant exposure to both asbestos and tobacco smoke: asbestos alone was associated with an approximate fivefold increase in lung cancer risk, smoking alone with about a 10-fold risk, and both exposures with about 50-fold above the unexposed
  • The authors stated that quantifying these risks is problematic because they depend on dose and time
  • Citing Vainio and Boffetta (1994), measures of the interaction showed considerable variation across studies, but studies of the highest exposures pointed to a multiplicative interaction
  • Whether asbestos-related fibrosis is central to lung cancer was described as controversial; reported excesses of lower lobe tumors and adenocarcinomas in exposed patients were not found by all studies
  • Proposed mechanisms from other studies included oxidative DNA damage, chromosome damage, and asbestos fibers delivering concentrated tobacco carcinogens to target cells
  • Molecular studies of lung tumors reported asbestos exposure associated with FHIT gene deletion (Nelson et al., 1998) and k-ras transversion mutations occurring in asbestos-exposed individuals without evidence of fibrotic alterations (Nelson et al., 1999)
  • p53 mutations and aberrant protein expression in lung cancer were associated with asbestos exposure in several cited studies
• The authors' conclusion: The authors concluded that molecular epidemiologic studies suggest combined exposure produces more mutations of the type caused by tobacco carcinogens than occur without asbestos exposure. They also concluded that these molecular changes may be independent of fibrosis, implying that the pathways for fibrosis and lung cancer are at least partly distinct.
• Limitations the authors state:
  • Molecular epidemiology studies are limited by their ability to estimate asbestos exposure
  • Separating the independent and joint effects of asbestos and tobacco requires large numbers of non-smoking asbestos-exposed individuals, and lung cancer in this group is becoming rarer in the United States
  • Epidemiologic data resources may not be adequate to answer whether fibrosis is part of the lung cancer pathway

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: Epidemiology, Lung Cancer, Asbestos Exposure, Reactive Oxygen Species (ROS), Epithelium, Fibrosis.

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