Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles

Our plain-English summary of Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles, by A.B. Kane (Inhalation Toxicology, 2000).

The study

• Author: A.B. Kane
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:133-40
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos fibers and crystalline silica are carcinogenic to humans when inhaled into the lungs. Asbestos fibers and cigarette smoke most likely act as cofactors in the induction of lung cancer. Point mutations in the K-ras oncogene and the p53 tumor-suppressor gene are frequent in lung cancers and are consistent with the known mutagenic spectrum of tobacco-smoke carcinogens. The FHIT tumor suppressor gene is also frequently inactivated in lung cancers of smokers and in workers who were exposed to asbestos. Recent molecular studies of p53 tumor suppressor gene mutations and p53 protein expression in the lungs of patients with lung cancer and occupational exposure to crystalline silica and other dusts have been conducted. Mutations in the p53 gene were detected at a frequency similar to those in smoking-related lung cancers. Expression of p53 protein can be detected by immunohisto-chemistry in preneoplastic epithelial lesions in the lungs of smokers and workers. Human malignant mesotheliomas frequently show overexpression of p53 protein; however, point mutations at the p53 tumor suppressor gene or ras oncogene locus are rare. Most cases of malignant mesotheliomas have codeletions of the p15 and p16 tumor suppressor genes and alterations at the NF2 tumor suppressor gene locus with monosomy of chromosome 22. The molecular alterations characteristic of malignant mesotheliomas may develop during later stages of tumor progression and may not reflect the direct genotoxic effects of fibers on the target cell population.

In plain English

This article was a review, which the author called an overview, of published research on gene changes in tumors linked to asbestos fibers and other inhaled particles such as crystalline silica. It reported no new data. Citing other studies, the author described K-ras gene mutations in 20-50% of lung adenocarcinomas. The author also described inactivation of the FHIT gene in lung cancers of smokers and of smokers exposed to asbestos. A cited study of lung cancer patients exposed to crystalline silica and other dusts found p53 mutations at a frequency similar to smoking-related lung cancers. Most patients in the cited studies were current or former smokers. For malignant mesothelioma, the reviewed studies reported that oncogene mutations were rare and that only 25% had p53 mutations or deletions. NF2 losses were found in 72% of cases, and the p16 gene was inactivated in 70-100% of cases. The author wrote that the mechanisms by which asbestos fibers cause these cancers are unknown. The author concluded that the gene changes may arise late in tumor progression and may not reflect direct genetic damage by fibers.

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 (overview) of published studies; no new data
• Who was studied: No study population of its own; the review drew on published molecular studies of human lung cancers and malignant mesotheliomas, with some rodent tumor studies
• Exposure: Asbestos fibers (no specific fiber types named), crystalline silica and other particulates, with cigarette smoke discussed as a cofactor for lung cancer
• Main results:
  • Cited studies: point mutations at codons 12 and 13 of the K-ras gene in 20-50% of lung adenocarcinomas, more common in smokers or ex-smokers
  • A cited study (Nelson et al., 1998): the FHIT tumor suppressor gene was inactivated in lung cancers of smokers and in smokers exposed to asbestos
  • A cited study of lung cancer patients with occupational exposure to crystalline silica and other dusts: p53 mutations at a frequency similar to smoking-related lung cancers. Most patients in the cited studies were current or former smokers, and no genetic lesions specific to crystalline silica had been identified
  • Cited studies of human malignant mesotheliomas: oncogene mutations were rare, and only 25% had point mutations or deletions of the p53 gene, although p53 protein was overexpressed in most
  • Cited study of malignant mesotheliomas: allelic losses at the NF2 gene locus in 72% of cases
  • Cited studies of malignant mesotheliomas: the p16 tumor suppressor gene was reported inactivated in 70-100% of cases
  • The author stated that the mechanisms by which asbestos fibers cause lung cancer and malignant mesothelioma are unknown
• The authors' conclusion: The author concluded that the molecular changes typical of lung tumors and malignant mesotheliomas may develop during later stages of tumor progression and may not reflect direct genotoxic effects of fibers on the target cells

Topics

Medical terms in this study, explained in our Lexicon: Tumor Suppressor Gene, Crystalline, Carcinogenic, Lung Cancer, Occupational Exposure, Mesothelioma.

Related studies

• Oncogenes and tumor-suppressor genes in mesothelioma--a synopsis — J.F. Lechner, J. Tesfaigzi, et al. (1997)
• Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf) — T. Chernova, F.A. Murphy, et al. (2017)
• Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling — G.J. Gordon, G.N. Rockwell, et al. (2005)
• LATS2 is a tumor suppressor gene of malignant mesothelioma — H. Murakami, T. Mizuno, et al. (2011)
• Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma — S.S. Murthy, J.R. Testa (1999)
• Recurring loss involving chromosomes 1, 3, and 22 in malignant mesothelioma: possible sites of tumor suppressor genes — W.L. Flejter, F.P. Li, et al. (1989)

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