Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis

Our plain-English summary of Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis, by A. Franko, M. Dodic-Fikfak, N. Arnerić, et al (Journal of Occupational and Environmental Medicine, 2007).

The study

• Authors: A. Franko, M. Dodic-Fikfak, N. Arnerić, V. Dolzan
• Journal: Journal of Occupational and Environmental Medicine
• Published: 2007;49(6):667-71
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: In a nested case-control study, the authors investigated whether the deletion polymorphism of glutathione S-transferases GSTM1 and GSTT1 represents a risk factor for the development of asbestosis.

Methods: In total, 262 cases with asbestosis and 265 controls, selected from a cohort of 2080 workers occupationally exposed to asbestos, were genotyped for GSTM1 and GSTT1-null alleles. Cumulative exposure for each subject was available.

Results: Asbestosis was associated with cumulative exposure (odds ratio [OR]=3.21, confidence interval [CI] 2.43-4.23) and GSTT1-null genotype (OR=0.61, CI 0.40-0.94), but not with GSTM1-null genotype (OR=1.01, CI 0.71-1.43). The risk of GSTM1-null and GSTT1-null genotype for asbestosis did not change after adjustment by cumulative exposure, smoking, gender, and age.

Conclusions: An important finding of this study is that GSTT1 gene deletion might have a protective effect on the development of asbestosis.

In plain English

This nested case-control study asked whether deletions of the glutathione S-transferase genes GSTM1 and GSTT1 were linked to asbestosis. The authors genotyped 262 workers with asbestosis and 265 workers with no asbestos disease. Controls were originally selected to match cases by age and gender, but in the final groups cases averaged 61 years and controls 57, a significant difference. All came from 2080 workers seen by a Slovenian asbestos-disease board in 1998–2003 and had worked at the Salonit Anhovo asbestos-cement plant. Mean cumulative asbestos exposure was 37.67 fibers/cm3-years in cases and 11.23 in controls. The GSTM1-null genotype (60.4% of cases, 60.6% of controls) was not associated with asbestosis (odds ratio 1.01, confidence interval 0.71–1.43). The GSTT1-null genotype was less common in cases (17.3%) than in controls (25.4%), giving an odds ratio of 0.61 (0.40–0.94). This changed little after adjustment for gender, age, cumulative exposure or smoking. The authors concluded that GSTT1 deletion might protect against asbestosis. They noted their method could not detect carriers of one deleted copy, and that about 26% of selected workers were excluded.

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: Nested case-control study (genetic association study)
• Who was studied: 262 workers with asbestosis (186 male, 76 female) and 265 controls with no asbestos disease (183 male, 82 female). They were selected from a cohort of 2080 workers presented at the Slovenian Board for the Recognition of Occupational Asbestos Diseases from January 1, 1998 to December 31, 2003. All had been employed at the Salonit Anhovo asbestos-cement plant in Slovenia. Controls were matched to cases by age and gender when the original 356 cases and 356 controls were selected. After exclusions, cases averaged 61 years and controls 57 years, a statistically significant difference.
• Exposure: Occupational asbestos exposure in an asbestos-cement manufacturing plant, covering cement production, asbestos-cement pipes and corrugated sheets. Exposure was expressed as cumulative exposure in fibers/cm3-years. It was built from a job exposure matrix based on more than 1000 air samples and on estimates. The genetic factors studied were the GSTM1-null and GSTT1-null genotypes. The article does not name the fiber types in this study.
• Main results:
  • In the final groups, workers with asbestosis averaged 61 years of age and controls 57 years. The difference was statistically significant.
  • Mean cumulative asbestos exposure was 37.67 fibers/cm3-years in workers with asbestosis and 11.23 fibers/cm3-years in controls. Mean duration of exposure was 267.62 months in cases and 229.80 months in controls. Both were significantly higher in cases.
  • Asbestosis was associated with cumulative exposure (odds ratio 3.21, confidence interval 2.43–4.23). The article does not state what exposure unit this odds ratio refers to.
  • The GSTM1-null genotype was found in 60.4% of cases (157 of 260) and 60.6% of controls (160 of 264). The difference was not significant. It was not associated with asbestosis (odds ratio 1.01, confidence interval 0.71–1.43).
  • The GSTT1-null genotype was found in 17.3% of cases (45 of 260) and 25.4% of controls (67 of 264). This difference was statistically significant.
  • The GSTT1-null genotype was associated with a lower risk of asbestosis (odds ratio 0.61, confidence interval 0.40–0.94).
  • After adjustment, the odds ratios for GSTT1-null were 0.62 (95% CI 0.40–0.94) for gender, 0.63 (0.40–0.97) for age, 0.60 (0.38–0.96) for cumulative exposure and 0.63 (0.41–0.97) for smoking. For GSTM1-null, the adjusted odds ratios stayed between 0.94 and 1.00, with confidence intervals including 1.
  • Smoking did not differ between groups: about 46% of both cases (117) and controls (120) were ever smokers.
• The authors' conclusion: The authors concluded that the GSTT1-null genotype was associated with a decreased risk of asbestosis, meaning that GSTT1 gene deletion might have a protective effect against developing asbestosis. They saw no association with GSTM1-null. They said further studies are needed on how this relates to lung cancer.
• Limitations the authors state:
  • The genotyping method could not detect heterozygous carriers of the GSTM1 or GSTT1 deletion (people with one deleted copy).
  • About 26% of selected cases and controls were excluded because they had died, developed a malignancy, or refused to take part. The authors reported no differences in cumulative exposure, duration of exposure, or cancer diagnosis between excluded and included subjects, and believed no bias was introduced.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), nested case-control study, Cumulative Exposure, Odds Ratio, confidence interval.

Related studies

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• Genetic polymorphism for glutathione-S-transferase mu in asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1994)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)
• Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases — A. Horska, C. Mislanova, et al. (2011)
• The influence of genetic polymorphisms of GSTP1 on the development of asbestosis — A. Franko, V. Dolzan, et al. (2008)
• The role of polymorphisms in glutathione-related genes in asbestos-related diseases — A. Franko, K. Goricar, et al. (2021)

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