Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma

Our plain-English summary of Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma, by R. Puntoni, R. Filiberti, P.G. Cerrano, et al (Mutation Research, 2003).

The study

• Authors: R. Puntoni, R. Filiberti, P.G. Cerrano, M. Neri, R. Andreatta, S. Bonassi
• Journal: Mutation Research
• Published: 2003;544(2-3):385-96
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The carcinogenic effect of asbestos has been reported in the literature since 40 years, and early studies describing the epidemic occurrence of malignant mesothelioma (MM) in asbestos workers, have become a paradigm of occupational cancer research. Research on MM was abandoned for many years since MM was considered as an asbestos-related disease, interesting only from a perspective of disease control and preventive policies. The introduction of new biological endpoints in the epidemiological studies has boosted research in the field, providing new tools for the study of emerging priority in cancer research and in public health. This approach, known as molecular epidemiology has a great potential in the study of MM, contributing to the understanding of susceptibility factors, to the evaluation of cancer risk in people occupationally or environmentally exposed to carcinogens, and to the enhancement of diagnosis and therapy. A comprehensive approach based on the use of banks of biological samples is presented and its advantages discussed here. The application of innovative endpoints, such as oncoproteins in biologic fluids, genetic polimorphisms, or gene function is discussed, and relevant literature reviewed.

In plain English

This article was a review and proposal. It argued for 'molecular epidemiology' studies of pleural malignant mesothelioma, which combine population research with laboratory measurements. These studies would rely on banks of stored samples from mesothelioma patients, lung cancer patients and two control groups. The authors reviewed published research on DNA repair, inherited variation in genes that process chemicals, cancer-related genes and proteins, and families with several mesothelioma cases. They also summarized their own group's work. In an earlier study, patients with pleural mesothelioma had significantly more micronuclei (a sign of chromosome damage) in blood cells than all comparison groups. Micronucleus frequency was not associated with asbestos exposure. In an interim analysis of 44 mesothelioma patients and 99 controls, no significant results were found. People with the deleted ('null') form of both the GSTM1 and GSTT1 genes were compared with people with a working form of either gene. The odds ratio for mesothelioma was 2.5 (95% CI 0.6–10.1), which was not statistically significant. Antibodies to the p53 protein were found only occasionally in patients' blood. The authors concluded that sample banks offer advantages for mesothelioma research.

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: Review and proposal of a research approach: molecular epidemiology based on banks of biological samples. It includes summaries of the authors' own published and unpublished results.
• Who was studied: There was no single study population. The article reviewed literature on pleural malignant mesothelioma. It described the authors' sample bank of mesothelioma and lung cancer patients plus two control groups. The first control group was people at risk for respiratory cancers, including patients with asbestosis, silicosis or lung disorders, and heavy smokers. The second was healthy blood donors and volunteers.
• Exposure: Asbestos; the text does not specify fiber type. Simian virus 40 (SV40) was also discussed as a possible co-factor.
• Main results:
  • In the authors' earlier micronucleus study, patients with pleural mesothelioma had a significantly higher micronucleus frequency in blood lymphocytes than all other groups. The other groups were lung cancer patients and two control groups. Lung cancer patients did not differ from the control groups. The text gives no numbers; they were shown in a figure.
  • In the same study, micronucleus frequency was not associated with sex, age, smoking status, pack-years, or asbestos exposure (including duration) in any group.
  • The authors' case-control study of metabolic gene variants (CYP1A1, mEH, GSTM1, GSTT1) had an interim analysis of an Italian population of 44 mesothelioma patients and 99 controls. No significant results were found.
  • In that interim analysis, people with both GSTT1 null and GSTM1 null genotypes were compared with people with a functional GSTM1 or GSTT1 genotype. The odds ratio for mesothelioma was 2.5 (95% CI 0.6–10.1), which was not statistically significant.
  • In the authors' analysis of p53 antibodies, detectable antibodies in the serum of mesothelioma patients appeared to be occasional. Two positive findings were reported among patients with benign lung diseases.
• The authors' conclusion: The authors concluded that their proposed approach shows the advantages of creating banks of biological samples for molecular epidemiology of mesothelioma. From their micronucleus data, they also concluded that asbestos exposure is not by itself a cause of the genetic instability that leads to micronucleus formation.
• Limitations the authors state:
  • The authors noted that cohort studies of mesothelioma require thousands of exposed people and very long follow-up.
  • The authors noted that case-control studies of mesothelioma may be unable to study markers that do not persist over time.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epidemiology, Malignant Mesothelioma, Carcinogenic.

Related studies

• Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies — M. Dusinska, M. Staruchova, et al. (2012)
• A molecular epidemiology case control study on pleural malignant mesothelioma — C. Bolognesi, F. Martini, et al. (2005)
• Smoking and the molecular epidemiology of lung cancer — D.C. Christiani (2000)
• The molecular epidemiology of asbestos and tobacco in lung cancer — H.H. Nelson, K.T. Kelsey (2002)
• A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma — S. Nishikawa, A. Tanaka, et al. (2014)
• SV40 enhances the risk of malignant mesothelioma among people exposed to asbestos: a molecular epidemiologic case-control study — A. Cristaudo, R. Foddis, et al. (2005)

Browse more research in Mutation Research, or return to medical research.