K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos

Our plain-English summary of K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos, by K. Husgafvel-Pursiainen, P. Hackman, M. Ridanpää, et al (International Journal of Cancer, 1993).

The study

• Authors: K. Husgafvel-Pursiainen, P. Hackman, M. Ridanpää, S. Anttila, A. Karjalainen, T. Partanen, O. Taikina-Aho, L. Heikkilä, H. Vainio
• Journal: International Journal of Cancer
• Published: 1993;53(2):250-6
• Cited by: 133 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed--in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation--a clear association of K-ras mutations with heavy life-time smoking (> or = 50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2-19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6-8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.

In plain English

This Finnish study looked for ras gene mutations in lung tumours removed at surgery from 48 patients at Helsinki University Central Hospital in 1988 to 1991. Smoking and work histories came from interviews, and asbestos fibres in healthy lung tissue were counted by electron microscopy. K-ras mutations were found in 14 of the 48 tumours (29%). No N-ras or H-ras mutations were found. Mutations were most frequent in adenocarcinoma (12 of 21, 57%). Heavy smoking (50 or more pack-years) was associated with having a K-ras mutation (odds ratio 4.9, 90% confidence interval 1.2 to 19.5). For patients with 3 million or more asbestos fibres per gram of dry lung tissue, which the authors treated as occupational exposure, the odds ratio was 2.2 (90% confidence interval 0.6 to 8.7), not statistically significant. All the heavily asbestos-exposed patients were current or former smokers, so the authors could not demonstrate an independent role for asbestos. The authors concluded that K-ras mutations were associated with heavy smoking, possibly in combination with occupational asbestos exposure.

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 (molecular) study of surgically removed lung tumours, combined with interview data on exposure and lung fibre counts; associations analysed by multivariate logistic regression and Mantel-Haenszel adjusted tables
• Who was studied: 48 lung cancer patients (42 male, mean age 62) who had lobectomy or pneumonectomy at Helsinki University Central Hospital, Finland, in 1988-1991. They were the patients with a tumour specimen out of 122 who came for suspected operable lung cancer. The tumours were 21 squamous-cell carcinomas, 21 adenocarcinomas, 2 large-cell carcinomas and 4 small-cell cancers.
• Exposure: Tobacco smoke, measured in pack-years and split at 50 pack-years. Asbestos, measured as pulmonary asbestos fibre concentration by transmission electron microscopy and split at 3 million fibres per gram of dry lung tissue, which the authors treated as occupational exposure. Occupational history came from interview. The authors state that mineralogical fibre type was determined but do not report the fibre types.
• Main results:
  • K-ras mutations were found in 14 of 48 tumours (29%); no N-ras or H-ras mutations were found.
  • Mutations were most frequent in adenocarcinoma (12 of 21, 57%); 2 of 21 squamous-cell carcinomas had a mutation.
  • K-ras mutation was associated with adenocarcinoma compared with the other tumour types: odds ratio 16.9, 90% CI 3.1-91.8.
  • Heavy smoking (50 or more pack-years) was associated with K-ras mutation in multivariate analysis: odds ratio 4.9, 90% CI 1.2-19.5.
  • Occupational-level asbestos fibre burden (3 million or more fibres per gram of dry lung) showed an odds ratio of 2.2 (90% CI 0.6-8.7) for K-ras mutation and 3.4 (90% CI 0.7-15.4) for adenocarcinoma type; neither was statistically significant.
  • When smoking and asbestos were each adjusted for the other, the odds ratio for K-ras mutation was 3.4 for heavy smoking and 2.0 for occupational asbestos exposure; both were non-significant.
  • Half of all mutations (7 of 14), and 7 of the 12 adenocarcinoma mutations, were in patients with large amounts of asbestos fibres in the lungs.
  • All but one mutation-positive tumour occurred in current or former heavy smokers (mean 57 pack-years, SD 23).
  • Mutation-positive tumours were found in younger patients: odds ratio 0.9 per 1-year increase in age, 90% CI 0.85-0.98.
• The authors' conclusion: The authors concluded that K-ras mutations are frequent in lung adenocarcinoma and are associated with heavy lifetime tobacco smoke exposure, possibly in combination with occupational asbestos exposure. They also concluded that an independent role for asbestos alone could not be significantly demonstrated.
• Limitations the authors state:
  • All the heavily asbestos-exposed patients were current or former smokers, so the authors could not show a significant independent role for asbestos fibre exposure.

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: Adenocarcinoma, Occupational Exposure, Lung Cancer, Lung Adenocarcinoma, Odds Ratio, Multivariate Analysis, Asbestos Exposure.

Related studies

• Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations — H. Vainio, K. Husgafvel-Pursiainen, et al. (1993)
• p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures — K. Husgafvel-Pursiainen, M. Ridanpää, et al. (1995)
• Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations — K. Husgafvel-Pursiainen, A. Karjalainen, et al. (1999)
• K-ras and rho A mutations in malignant pleural effusion — M. Nakamoto, H. Teramoto, et al. (2001)
• Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression — D.G. Guinee, W.D. Travis, et al. (1995)
• Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos — Z. Ni, Y. Liu, et al. (2000)

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