Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations

Our plain-English summary of Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations, by H. Vainio, K. Husgafvel-Pursiainen, S. Anttila, et al (Environmental Health Perspectives, 1993).

The study

• Authors: H. Vainio, K. Husgafvel-Pursiainen, S. Anttila, A. Karjalainen, P. Hackman, T. Partanen
• Journal: Environmental Health Perspectives
• Published: 1993;101 Suppl 3(Suppl 3):189-92
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

To investigate the role of tobacco smoking and asbestos fibers in the etiology of human lung cancer, we examined the activating point mutations in the K-ras oncogene in DNA samples from 49 patients. Mutations were found more often in tissue from adenocarcinomas (12/21) than in tissue from tumors other than nonadenocarcinomas of the lung (3/28). Among the adenocarcinoma patients, asbestos exposure was predictive of K-ras mutation (odds ratio, 4.9; 95% confidence interval, 0.7-34.3); in patients with other types of lung cancer, the relation appeared to be an inverse one, but the numbers were small. The proportion of heavy smokers (over 50 pack-years) was 60% among people with K-ras mutations and 35% among the K-ras-negative subjects, suggesting that smoking causes K-ras mutations. If mutations in K-ras genes are caused by smoking, asbestos would act as a promoting agent by conferring selective growth conditions for clonal expansion on these mutated cells. Asbestos may favor recruitment of (initiated) K-ras mutation-positive cells in the multistage process of carcinogenesis by stimulating cellular growth.

In plain English

This study examined surgically removed tumor tissue from 49 lung cancer patients at Helsinki University Hospital, 21 of them adenocarcinomas. The authors tested tumor DNA for K-ras gene mutations. They measured lung asbestos fibers by electron microscopy, counting over 3 million fibers per gram of dried lung as heavy, occupational-level exposure. Heavy exposure appeared in 9 of 21 adenocarcinomas and 5 of 28 other cases. K-ras mutations were found in 12 of 21 adenocarcinomas and 3 of 28 other tumors. Among adenocarcinoma patients, heavy exposure went with K-ras mutation, not statistically significantly (odds ratio 4.9; 95% confidence interval 0.7 to 34.3). Compared with patients with low fiber counts and no mutation, those with both heavy exposure and a mutation had an odds ratio for adenocarcinoma, versus other lung cancer types, of 41.0 (95% confidence interval 2.1 to 809). Heavy smokers (over 50 pack-years) were 60% of smokers with mutations and 35% of those without, a nonsignificant difference. The authors concluded that smoking may cause the mutations and asbestos may promote growth of mutated cells. They noted the small numbers.

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: Laboratory and epidemiological analysis of surgically removed lung tumors (K-ras mutation testing and lung fiber counts), analyzed by logistic regression (case-referent type) and tabular analysis
• Who was studied: 49 lung cancer patients whose tumors were removed by thoracotomy at Helsinki University Hospital, Finland: 21 adenocarcinomas, 22 squamous cell, 4 small cell and 2 large cell carcinomas. Study dates not given.
• Exposure: Asbestos fiber concentration in lung tissue, measured by transmission electron microscopy. More than 3 million fibers per gram of dried lung was taken to indicate occupational (heavy) asbestos exposure. Fiber types are not reported. Smoking was measured in pack-years.
• Main results:
  • Heavy asbestos exposure (over 3 million fibers per gram of dried lung) was found in 9 (43%) of 21 adenocarcinoma cases and 5 (17%) of 28 non-adenocarcinoma cases. The odds ratio for adenocarcinoma with heavy exposure was 3.5 (95% CI 0.9-12.6).
  • K-ras mutations were found in 12 (57%) of adenocarcinomas and 3 (11%) of non-adenocarcinoma lung cancers. The odds ratio for adenocarcinoma in K-ras-positive tumors was 11.1 (95% CI 2.54-45.3).
  • Among adenocarcinoma patients, heavy asbestos exposure was predictive of K-ras mutation, but not significantly (odds ratio 4.9; 95% CI 0.7-34.3).
  • In other lung cancer cell types the relation appeared inverse, but numbers were small.
  • Compared with patients with low fiber counts and no K-ras mutation, the odds ratio for adenocarcinoma (versus other cell types) was 41.0 (95% CI 2.1-809) in patients with heavy asbestos exposure and a K-ras mutation (7 adenocarcinomas, 0 other cancers).
  • For patients with lower fiber content and a K-ras mutation, the odds ratio for adenocarcinoma was 4.8 (95% CI 0.9-25.3), not quite statistically significant. For patients with high asbestos exposure but no mutation it was near unity (Table 4: 1.14, 95% CI 0.18-7.28).
  • Among smokers, heavy smokers (over 50 pack-years) made up 60% of those with K-ras mutations and 35% of K-ras-negative subjects. The odds ratio was 2.8, nonsignificant (Table 5: 2.81, 95% CI 0.61-13.0).
• The authors' conclusion: The authors concluded that tobacco smoke appears to be a factor in causing K-ras mutations in lung adenocarcinoma. They concluded that asbestos, which does not itself cause point mutations, appears to increase the likelihood of K-ras mutations in adenocarcinomas, possibly by increasing cell proliferation and the recruitment of mutated cells into the carcinogenic process.
• Limitations the authors state:
  • The authors noted that the numbers were small, specifically for the analysis in non-adenocarcinoma cell types.

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 Adenocarcinoma, Etiology, Lung Cancer, Adenocarcinoma, Asbestos Exposure, Odds Ratio, confidence interval, Carcinogenesis.

Related studies

• K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos — K. Husgafvel-Pursiainen, P. Hackman, et al. (1993)
• Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure — T. Sioris, K. Husgafvel-Pursiainen, et al. (2000)
• Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations — K. Husgafvel-Pursiainen, A. Karjalainen, et al. (1999)
• p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures — K. Husgafvel-Pursiainen, M. Ridanpää, et al. (1995)
• A somatic TSHR mutation in a patient with lung adenocarcinoma with bronchioloalveolar carcinoma, coronary artery disease and severe chronic obstructive pulmonary disease — J.W. Kim, S. Lee, et al. (2012)
• Pulmonary adenocarcinoma with epidermal growth factor receptor-mutations in asbestos exposed non-smokers: A case series — R.L. Kradin, J. Iafrate, et al. (2017)

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