The role of polymorphisms in glutathione-related genes in asbestos-related diseases

Our plain-English summary of The role of polymorphisms in glutathione-related genes in asbestos-related diseases, by A. Franko, K. Goricar, M. Dodic Fikfak, et al (Radiology and Oncology, 2021).

The study

• Authors: A. Franko, K. Goricar, M. Dodic Fikfak, V. Kovac, V. Dolzan
• Journal: Radiology and Oncology
• Published: 2021;55(2):179-186
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The study investigated the influence of GCLC, GCLM, GSTM1, GSTT1 and GSTP1 polymorphisms, as well as the influence of interactions between polymorphism and interactions between polymorphisms and asbestos exposure, on the risk of developing pleural plaques, asbestosis and malignant mesothelioma (MM).

Subjects And Methods: The cross sectional study included 940 asbestos-exposed subjects, among them 390 subjects with pleural plaques, 147 subjects with asbestosis, 225 subjects with MM and 178 subjects with no asbestos-related disease. GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272 genotypes were determined using PCR based methods. In statistical analysis, logistic regression was used.

Results: GSTT1 null genotype was associated with the decreased risk for pleural plaques (OR = 0.63; 95% CI = 0.40-0.98; p = 0.026) and asbestosis (OR = 0.51; 95% CI = 0.28-0.93; p = 0.028), but not for MM. A positive association was found between GSTP1 rs1695 AG + GG vs. AA genotypes for MM when compared to pleural plaques (OR = 1.39; 95% CI = 1.00-1.94; p = 0.049). The interactions between different polymorphisms showed no significant influence on the risk of investigated asbestos-related diseases. The interaction between GSTT1 null polymorphism and asbestos exposure decreased the MM risk (OR = 0.17; 95% CI = 0.03-0.85; p = 0.031).

Conclusions: Our findings suggest that GSTT1 null genotype may be associated with a decreased risk for pleural plaques and asbestosis, may modify the association between asbestos exposure and MM and may consequently act protectively on MM risk. This study also revealed a protective effect of the interaction between GSTP1 rs1695 polymorphism and asbestos exposure on MM risk.

© 2021 Alenka Franko, Katja Goricar, Metoda Dodic Fikfak, Viljem Kovac, Vita Dolzan, published by Sciendo.

In plain English

This Slovenian cross-sectional study examined whether variants in five glutathione-related genes (GCLC, GCLM, GSTM1, GSTT1 and GSTP1) were linked to asbestos-related disease. It included 940 asbestos-exposed people: 390 with pleural plaques, 147 with asbestosis, 225 with malignant mesothelioma, and 178 controls with no asbestos-related disease. Compared with controls, people lacking the GSTT1 gene (the 'null genotype') had lower odds of pleural plaques (odds ratio 0.63; 95% CI 0.40 to 0.98) and asbestosis (0.51; 0.28 to 0.93), but not of mesothelioma. GSTP1 rs1695 AG or GG versus AA genotypes were linked to higher mesothelioma odds only when mesothelioma was compared with pleural plaques (1.39; 1.00 to 1.94). GCLC, GCLM and GSTM1 showed no associations. GSTT1 null status had no independent link with mesothelioma. However, its interaction with medium or high versus low asbestos exposure was associated with lower mesothelioma risk (interaction odds ratio 0.17; 0.03 to 0.85). The authors concluded that GSTT1 null may be associated with decreased risk of plaques and asbestosis, and may modify the exposure-mesothelioma association and so act protectively. They noted that exposure data were missing for many subjects, especially mesothelioma patients.

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: cross-sectional genetic association study using logistic regression
• Who was studied: 940 asbestos-exposed subjects in Slovenia: 390 with pleural plaques, 147 with asbestosis, 225 with malignant mesothelioma (pleural or peritoneal) and 178 with no asbestos-related disease (controls). Non-mesothelioma subjects were occupationally exposed and were presented to the State Board for the Recognition of Occupational Asbestos Diseases in 1998–2007. Mesothelioma patients were treated at the Institute of Oncology Ljubljana in 2004–2018.
• Exposure: Occupational asbestos exposure (fiber type not stated), grouped by cumulative exposure as low (under 11 fibres/cm3-years), medium (11 to 20) or high (over 20). For mesothelioma patients without measured cumulative exposure, exposure was estimated from work history. Six genetic variants were studied: GCLC rs17883901, GCLM rs41303970, GSTM1 null, GSTT1 null, GSTP1 rs1695 and GSTP1 rs1138272.
• Main results:
  • GSTT1 null genotype was associated with decreased odds of pleural plaques versus no disease (OR 0.63; 95% CI 0.40 to 0.98; p given as 0.026 in the text).
  • GSTT1 null genotype was associated with decreased odds of asbestosis versus no disease (OR 0.51; 95% CI 0.28 to 0.93; p = 0.028), but not with mesothelioma.
  • GSTP1 rs1695 AG plus GG versus AA genotypes were associated with higher odds of mesothelioma when compared with pleural plaques (OR 1.39; 95% CI 1.00 to 1.94; p = 0.049).
  • After adjustment for asbestos exposure and age, the GSTP1 rs1695 AG plus GG versus AA odds ratio for mesothelioma compared with pleural plaques was 1.97 (95% CI 1.14 to 3.39; p = 0.015).
  • No association was found between the GCLC rs17883901 or GCLM rs41303970 polymorphisms and asbestos-related diseases.
  • No association was found between GSTM1 null genotype and asbestos-related diseases.
  • High and medium versus low asbestos exposure was associated with asbestosis (OR 3.22; 95% CI 1.99 to 5.20; p less than 0.001).
  • High and medium versus low asbestos exposure was associated with mesothelioma (OR 4.06; 95% CI 2.28 to 7.23; p less than 0.001).
  • Interactions between the different polymorphisms showed no significant influence on the risk of the diseases studied.
  • The interaction term between high and medium versus low asbestos exposure and GSTT1 null genotype was associated with decreased mesothelioma risk (OR 0.17; 95% CI 0.03 to 0.85; p = 0.031).
  • GSTT1 null genotype on its own showed no independent association with mesothelioma compared with controls with no asbestos-related disease.
  • When mesothelioma was compared with pleural plaques, the interaction of asbestos exposure with GSTT1 null (OR 0.11; 95% CI 0.02 to 0.49) and with GSTP1 rs1695 (OR 0.14; 95% CI 0.03 to 0.65) was associated with decreased mesothelioma risk.
• The authors' conclusion: The authors concluded that GSTT1 null genotype may be associated with a decreased risk of pleural plaques and asbestosis, may modify the association between asbestos exposure and mesothelioma, and may consequently act protectively on mesothelioma risk.
• Limitations the authors state:
  • Asbestos exposure data were not available for all subjects, especially mesothelioma patients.
  • As a result, the gene-exposure interaction analyses could be done only for a subgroup of mesothelioma patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Asbestos Exposure, Pleural Plaques, Malignant Mesothelioma.

Related studies

• Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California — S.J. London, A.K. Daly, et al. (1995)
• Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2007)
• The influence of genetic polymorphisms of GSTP1 on the development of asbestosis — A. Franko, V. Dolzan, et al. (2008)
• Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases — A. Horska, C. Mislanova, et al. (2011)
• Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers — J.Y. Choi, M.L. Neuhouser, et al. (2007)
• Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study — I. Dianzani, L. Gibello, et al. (2006)

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