Polymorphisms in glutathioneS-transferases in French vinyl chloride workers

Abstract

The authors have recently demonstrated a significant gene-environment interaction between vinyl chloride exposure and polymorphisms in the DNA repair protein XRCC1 on the occurrence of mutant p53 biomarkers of vinyl chloride-induced genetic damage. The aim of this study was to examine the polymorphisms in the glutathione S-transferases (GSTs) as potential modifiers of this relationship, since these enzymes may be involved in the phase II metabolism of the reactive intermediates of vinyl chloride. A cohort of 211 French vinyl chloride workers was genotyped for common polymorphisms in GSTM1, GSTT1 and GSTP1. Although no independent, statistically significant effect of these polymorphisms on the occurrence of the mutant p53 biomarker was found, the null GSTM1 and null GSTT1 polymorphisms were found to interact with the XRCC 1 polymorphism to increase the occurrence of the biomarker such that, for example, workers with at least one variant XRCC1 allele who were null for both GSTM1 and GSTT1 had a significant odds ratio for the biomarker (OR =8.4, 95% CI = 1.3 54.0) compared with workers who were wild-type for all alleles, controlling for potential confounders including cumulative vinyl chloride exposure.

Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud’s phenomenon in French vinyl chloride monomer-exposed workers

“…Other enzymatic systems are involved in the metabolism and toxicity of VCM, and they could have a more important role or interact with each other, masking the individual effect of GSTs or influencing the impact of their activity. A previous analysis of another sample from the same French cohort of VCM workers, exposed to VCM in similar conditions, focused on the modifying role of polymorphic GST M1, GST T1 and GST P1 on the occurrence of mutant p53 biomarkers of VCM-induced genetic damage (Li et al 2005). GST M1-null and GST T1-null genotypes were found to have a number of nonsignificant effects, whereas they significantly interacted with DNA repair protein genotypes (X-ray crosscomplementing-1 protein, XRCC1) to increase the occurrence of the biomarker (Li et al 2005).…”

“…Such studies have mainly concerned liver lesions and carcinogenic processes, with none conducted about RP (Huang et al 1997;Wong et al 1998Wong et al , 2002Li et al 2005;Zhu et al 2005).…”

Genetic Polymorphisms in Metabolizing Enzymes and Susceptibility of Chromosomal Damage Induced by Vinyl Chloride Monomer in a Chinese Worker Population

“…Previously, many studies have been conducted to investigate the genotoxicity of VCM and the effect of genetic polymorphisms of genes involved in metabolism (CYP2E1, GSTs, ADH2, ALDH2) and DNA repair (XRCC1, XPD). 8,[12][13][14][15][16][17][18] To the best of our knowledge, however, there have been few investigations of the effect of genetic polymorphisms of genes involved in metabolism on CBMN frequencies in VCM workers. So CBMN was used in this study to monitor a group of subjects occupationally exposed to VCM, and the subjects were genotyped for several metabolizing genes: GSTT1 (gene deletion), GSTM1 (gene deletion), CYP2E1G/C (rs3813867), CYP2D6G/C (rs1135840), and GSTP1G/A (rs1695).…”

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

“…Many studies have investigated the effect of genetic polymorphisms of genes involved in metabolism (CYP2E1, GST, mEH, ALDH2) and DNA repair (XRCC1, XPD; refs. 6,[9][10][11][12][13][14][15]. To the best of our knowledge, however, no studies have been conducted on the effect of genetic polymorphisms of genes involved in cell cycle control.…”