A molecular epidemiology case control study on pleural malignant mesothelioma

Our plain-English summary of A molecular epidemiology case control study on pleural malignant mesothelioma, by C. Bolognesi, F. Martini, M. Tognon, et al (Cancer Epidemiology, Biomarkers & Prevention, 2005).

The study

• Authors: C. Bolognesi, F. Martini, M. Tognon, R. Filiberti, M. Neri, E. Perrone, E. Landini, P.A. Canessa, G.P. Ivaldi, P. Betta, L. Mutti, R. Puntoni
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2005;14(7):1741-6
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural malignant mesothelioma is an uncommon neoplasm usually associated with asbestos exposure. The increasing incidence of malignant mesothelioma cases involving individuals with low levels of asbestos exposure suggests a complex carcinogenetic process with the involvement of other cofactors. Cytogenetic studies revealed the complexity of the genetic changes involved in this neoplasm reflecting the accumulation of genomic damage. One of the most used methodologies for assessing genomic damage is the cytokinesis-blocked micronucleus test applied in peripheral blood lymphocytes (PBL). This approach allows the detection of chromosomal alterations expressed in binucleated cells after nuclear division in vitro. This marker could provide a tool for assessing genetically determined constitutional differences in chromosomal instability. A biomonitoring study was carried out to evaluate the micronuclei frequency in PBLs of patients with pleural malignant mesothelioma with respect to lung cancer, healthy, and risk controls as a marker of cancer susceptibility in correlation with the presence of SV40. A significant increased micronuclei frequency was observed in patients with malignant mesothelioma in comparison with all the other groups, the mean micronuclei frequency was double in patients with malignant mesothelioma compared with healthy controls, risk controls, and patients with lung adenocarcinoma (median 11.4 binucleated cells with micronuclei/1,000 binucleated cells versus 6.2, 6.1, and 5.1, respectively). Our data indicate that human T lymphocyte samples carry DNA sequences coding for SV40 large T antigen at low prevalence, both in cancer cases and controls. Evidence of cytogenetic damage revealed as micronuclei frequency in mesothelioma cancer patients could be related to exogenous and endogenous cofactors besides asbestos exposure.

In plain English

This case-control study from northwestern Italy measured micronuclei in blood lymphocytes. Micronuclei are chromosome fragments or whole chromosomes left outside the cell nucleus, used as a sign of chromosome damage. Between March 1996 and August 2000 the authors enrolled 21 patients with pleural malignant mesothelioma, 37 with lung cancer, 33 with benign respiratory diseases (at-risk controls) and 62 healthy controls, in areas with asbestos exposure from industry. Asbestos exposure was assessed by interview. The mesothelioma patients had a significantly higher median micronuclei frequency (11.4 per 1,000 binucleated cells) than lung cancer patients (5.1), at-risk controls (6.1) and healthy controls (6.2). Within each group, micronuclei did not differ between people with and without past asbestos exposure, and no link with smoking status was seen. SV40 virus DNA was found in 4 of 59 tested lymphocyte samples (two mesothelioma, two lung cancer). None was positive for JC virus. The authors concluded that malignant mesothelioma was associated with a statistically significant increase in micronuclei, which might be related to individual susceptibility. They said the results need confirming in a larger population.

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 case-control (biomonitoring) study comparing micronuclei frequency in blood lymphocytes across four groups, with PCR testing for SV40 and JC virus sequences
• Who was studied: 21 patients with pleural malignant mesothelioma, 37 with lung cancer, 33 with benign respiratory diseases (at-risk controls, mostly chronic obstructive pulmonary disease) and 62 healthy controls, enrolled March 1996 to August 2000 in Genova, Casale and La Spezia, northwestern Italy
• Exposure: Past asbestos exposure, assessed by questionnaire according to the type of activity and the length of exposure. No fiber types were specified. Reported exposure: 19 of 21 mesothelioma patients (90.5%), 7 of 37 lung cancer patients (18.9%), 5 of 33 at-risk controls (15.2%) and 5 of 62 healthy controls (8.1%). Among mesothelioma patients, exposure length ranged from 8 to 46 years, in jobs such as carpenter, insulator, docker and metallurgic work.
• Main results:
  • Median micronuclei frequency was 11.4 per 1,000 binucleated cells in mesothelioma patients, versus 5.1 in lung cancer patients (P less than 0.0001), 6.1 in at-risk controls (P = 0.002) and 6.2 in healthy controls (P less than 0.0001)
  • The differences remained significant (P less than or equal to 0.001) when only histologically confirmed mesothelioma cases were considered (median 12.1)
  • Using a cutoff of 14.2 per 1,000 binucleated cells (healthy-control mean plus 2 SD), 8 of 21 mesothelioma patients (38%) were above it, versus 0 of 37 lung cancer patients, 3 of 33 at-risk controls (9%) and 4 of 62 healthy controls (6%)
  • Within each group, micronuclei distribution did not differ between subjects with and without previous asbestos exposure
  • No correlation was seen between micronuclei frequency and smoking status
  • SV40 Tag sequences were found in 4 of 59 T lymphocyte samples (6.8%): two from mesothelioma patients and two from lung cancer patients. No sample was JC virus-positive.
• The authors' conclusion: The authors concluded that malignant mesothelioma is associated with a statistically significant increase in micronuclei frequency, with no evident relationship to intensity of asbestos exposure, smoking habits or polyoma virus. They suggested the cytogenetic damage might be related to individual susceptibility.
• Limitations the authors state:
  • The results need to be confirmed in a larger population of cancer patients
  • Most subjects fell in a relatively narrow age range, so an age effect could not be fully seen
  • Few women were recruited, which probably explains why the higher micronuclei frequency in females was not significant

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, Neoplasm, Asbestos Exposure, Micronuclei, Lung Cancer, SV40, Lung Adenocarcinoma.

Related studies

• 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)
• 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)
• The molecular epidemiology of asbestos and tobacco in lung cancer — H.H. Nelson, K.T. Kelsey (2002)
• Implementation of a molecular epidemiology approach to human pleural malignant mesothelioma — R. Puntoni, R. Filiberti, et al. (2003)
• Smoking and the molecular epidemiology of lung cancer — D.C. Christiani (2000)
• No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients — Z. Mohammad-Taheri, S.A. Nadji, et al. (2013)

Browse more research in Cancer Epidemiology, Biomarkers & Prevention, or return to medical research.