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Published on: January 12, 2020
Polymorphisms in glutathione S-transferases in French vinyl chloride workers
Y Li1, M Zhou, M J Marion
1Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 60 Haven Avenue, B-1, New York, NY 10032, USA.
Summary
Glutathione S-transferase polymorphisms modify vinyl chloride
Area of Science:
- Environmental Epigenetics
- Occupational Toxicology
- Genetic Epidemiology
Background:
- Vinyl chloride (VC) exposure is linked to genetic damage, indicated by mutant p53 biomarkers.
- Gene-environment interactions, specifically with DNA repair gene XRCC1 polymorphisms, influence VC-induced damage.
- Glutathione S-transferases (GSTs) are crucial for metabolizing reactive intermediates of VC, suggesting a role in modifying VC toxicity.
Purpose of the Study:
- To investigate the role of glutathione S-transferase (GST) polymorphisms (GSTM1, GSTT1, GSTP1) in modifying the gene-environment interaction between vinyl chloride exposure and XRCC1 polymorphisms.
- To assess the impact of GST polymorphisms on the occurrence of mutant p53 biomarkers in vinyl chloride-exposed workers.
Main Methods:
- Genotyping of 211 French vinyl chloride workers for common polymorphisms in GSTM1, GSTT1, and GSTP1.
- Analysis of the interaction between GST polymorphisms and XRCC1 polymorphisms concerning mutant p53 biomarker occurrence.
- Statistical control for potential confounders, including cumulative vinyl chloride exposure.
Main Results:
- No independent significant effect of GST polymorphisms on mutant p53 biomarker occurrence was observed.
- Null GSTM1 and null GSTT1 polymorphisms interacted significantly with XRCC1 polymorphisms.
- Workers with variant XRCC1 alleles and null for both GSTM1 and GSTT1 showed a significantly increased odds ratio (OR = 8.4) for the biomarker compared to wild-type individuals.
Conclusions:
- GSTM1 and GSTT1 null genotypes act as modifiers, amplifying the risk of vinyl chloride-induced genetic damage in the presence of XRCC1 variant alleles.
- Combined genetic susceptibility, involving DNA repair (XRCC1) and metabolic enzymes (GSTM1, GSTT1), is critical in determining individual risk from vinyl chloride exposure.
- These findings highlight the complex interplay of genetic factors in occupational carcinogenesis.
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