Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations

Our plain-English summary of Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations, by K. Husgafvel-Pursiainen, A. Karjalainen, A. Kannio, et al (American Journal of Respiratory Cell and Molecular Biology, 1999).

The study

• Authors: K. Husgafvel-Pursiainen, A. Karjalainen, A. Kannio, S. Anttila, T. Partanen, A. Ojajärvi, H. Vainio
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1999;20(4):667-74
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Studies on somatic mutations in lung cancers associated with cigarette smoking and asbestos exposure are few. We investigated prevalence of mutations in the p53 and K-ras genes in lung tumors from smokers with and without asbestos exposure at work. For K-ras mutations, the study was an extension of an earlier analysis. Nearly all of the 105 consecutive patients examined were smokers and had non-small-cell carcinoma of the lung with squamous-cell carcinoma or adenocarcinoma histology. Exposure to asbestos was estimated by pulmonary fiber counts and occupational histories. A pulmonary burden of >/= 1 x 10(6) asbestos fibers per gram of lung tissue, indicating work-related exposure, was found in 32% of the patients for whom fiber-analysis data were available (33 of 102 patients, all men). The statistical analysis showed pulmonary fiber count as the only significant predictor of adenocarcinoma histology, in contrast to squamous-cell carcinoma (smoking-adjusted odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1 to 8.5). The frequency of p53 mutations was 39% (13 of 33) among the asbestos-exposed cases, as compared with 54% (29 of 54) among the nonexposed cases; the difference was not significant, however. In male ever-smokers, a long duration of smoking was associated with p53 mutation (OR 3.2, 95% CI 1.2 to 8.8). In adenocarcinoma, p53 mutations were less prevalent (10 of 30, 33%) as compared with squamous-cell carcinoma (28 of 46, 61%; P = 0.02), whereas a strong and significant association was found between adenocarcinoma and K-ras mutation (OR 37, 95% CI 5.8 to 232, adjusted for smoking and asbestos exposure). Asbestos exposure alone was not significantly associated with increased occurrence of K-ras mutations. In conclusion, the results may primarily reflect the observed excess of adenocarcinoma in the asbestos- exposed patients, and hence the decrease in p53 mutations and increase in K-ras mutations.

In plain English

This Finnish study examined lung tumors from 105 consecutive surgical lung cancer patients, nearly all smokers, at Helsinki University Hospital between 1988 and 1992. The authors compared p53 and K-ras gene mutations in men with and without past work exposure to asbestos, judged from amphibole fiber counts in lung tissue and work histories. Thirty-three of the 102 patients with fiber data, all men, had 1 million or more fibers per gram of dry lung, taken to indicate work exposure. Among these men, 48% of tumors were adenocarcinomas and 42% squamous-cell carcinomas, against 26% and 59% in non-exposed cases. After adjusting for smoking, exposed men had higher odds of adenocarcinoma rather than squamous-cell carcinoma (odds ratio 3.0, 95% CI 1.1 to 8.5). p53 mutations were found in 39% (13 of 33) of exposed men and 54% (29 of 54) of non-exposed men, not a statistically significant difference. K-ras mutations were strongly linked to adenocarcinoma but not significantly to asbestos after adjustment. The authors concluded that the mutation differences may at least partly reflect the higher share of adenocarcinoma among exposed men.

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: Molecular epidemiology study of tumor samples from a consecutive series of surgical lung cancer patients, using logistic regression to relate gene mutations and tumor type to asbestos and smoking indicators
• Who was studied: 105 consecutive lung cancer patients (89 men, 16 women) operated on at Helsinki University Hospital, Finland, between August 1988 and October 1992. Of the 101 with detailed smoking data, 62 were current smokers, 35 had stopped at least one year before surgery, and 4 had never smoked. The statistical analyses included men only.
• Exposure: Past occupational asbestos exposure, estimated in two ways: from amphibole fiber concentration in lung tissue, measured by scanning electron microscopy, and from interview-based work histories rated by two occupational hygienists. Anthophyllite (spelled 'Antophyllite' in the article) was the main fiber type found. Chrysotile is poorly detected by this method. A concentration of 1.0 million fibers per gram of dry tissue or more was taken as indicating occupational exposure. Smoking amount, duration, starting age and time since quitting were also analyzed.
• Main results:
  • 33 of the 102 patients with fiber data (32%, all men) had 1 million or more amphibole fibers per gram of dry lung tissue. Job histories classified 30 of these 33 as definitely, probably or possibly exposed. Seven of them had asbestosis.
  • Among exposed men, 48% of tumors were adenocarcinomas and 42% squamous-cell carcinomas, compared with 26% and 59% in non-exposed cases. In ever-smoking men, a fiber count of 1 million or more per gram was the only significant predictor of adenocarcinoma rather than squamous-cell carcinoma (smoking-adjusted OR 3.0, 95% CI 1.1 to 8.5). This odds ratio compares exposed with non-exposed men.
  • p53 mutations were found in 39% (13 of 33) of occupationally exposed men and 54% (29 of 54) of non-exposed men. Among men with more than 5 million fibers per gram, the figure was 20% (2 of 10). The difference was not statistically significant.
  • In male ever-smokers, smoking for more than 43 years was a statistically significant predictor of p53 mutation in the univariate analysis (OR 3.23, 95% CI 1.19 to 8.79). In the multivariate analysis the OR was 2.87 (95% CI 0.98 to 8.40).
  • p53 mutations were less common in adenocarcinoma (10 of 30, 33%) than in squamous-cell carcinoma (28 of 46, 61%), with P = 0.02 (printed as 'P 5 0.02'). The authors state that all P values are one-sided.
  • K-ras mutations were found in 21% (20 of 97) of tumors. In men, adenocarcinoma was strongly associated with K-ras mutation (OR 37, 95% CI 5.8 to 232, adjusted for smoking and asbestos exposure).
  • K-ras mutations were found in 33% (10 of 30) of exposed cases and 17% (9 of 54) of non-exposed cases, with P = 0.07 (printed as 'P 5 0.07'). After adjustment, the OR for asbestos exposure was close to 1 (1.02, 95% CI 0.22 to 4.71).
  • In non-exposed smokers, 31% (10 of 32) of p53 mutations were at lung cancer hot-spot codons. In the asbestos-exposed cases, only one mutation (8%) was at such a codon.
• The authors' conclusion: The authors proposed that the differences in p53 and K-ras mutation frequencies between asbestos-exposed and non-exposed lung cancer cases may, at least partially, reflect the relative increase of adenocarcinoma among the exposed cases.
• Limitations the authors state:
  • None of the female patients had been exposed to asbestos at work, so the analyses were restricted to men. Only surgical cases with adenocarcinoma or squamous-cell carcinoma were analyzed. As a result, no direct conclusions can be drawn for women or for small-cell lung cancer.
  • Chrysotile fibers are poorly detected by the electron microscopy method used, so the fiber counts represent amphibole fibers only.
  • Because patients were selected for surgery, small-cell lung cancers made up a smaller share than among lung cancer patients in general.

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, Occupational Exposure, Somatic Mutation, Asbestos Exposure, Carcinoma, Adenocarcinoma, Histology, Fibers Per Gram.

Related studies

• p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures — K. Husgafvel-Pursiainen, M. Ridanpää, et al. (1995)
• 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)
• 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)
• Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos — Z. Ni, Y. Liu, et al. (2000)
• Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations — H. Vainio, K. Husgafvel-Pursiainen, et al. (1993)
• Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients — S. Mäki-Nevala, M. Rönty, et al. (2014)

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