XRCC1 and CYP2E1 polymorphisms as susceptibility factors of plasma mutant p53 protein and anti-p53 antibody expression in vinyl chloride monomer-exposed polyvinyl chloride workers
Journal
Cancer Epidemiology Biomarkers and Prevention
Journal Volume
11
Journal Issue
5
Pages
475-482
Date Issued
2002
Author(s)
Abstract
Mutant p53 protein and anti-p53 antibody in circulating blood can be detected among individuals with mutations of the p53 tumor suppressor gene. Plasma mutant p53 protein and anti-p53 antibody have also been associated with vinyl chloride monomer (VCM) exposure, although the mechanism of VCM-related carcinogenesis remains unclear. Polymorphisms of metabolic and DNA repair genes have been implicated in chemical exposure -related carcinogenesis. The aim of this study is to explore the association between polymorphisms of metabolic and DNA repair genes with mutant p53 protein and anti-p53 antibody expression induced by VCM. Study subjects comprised 333 male workers occupationally exposed to VCM. Plasma mutant p53 protein and anti-p53 antibody detected with ELISA were grouped together as p53 overexpression. Genotypes of cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), glutathione S-transferase T1 (GSTT1), and X-ray repair cross -complementing group 1 (XRCC1, exon 10) genes were identified by the PCR. High VCM exposure group had significantly higher p53 overexpression as compared with low exposure group [odds ratio (OR), 2.1; 95% confidence interval (CI), 1.1-3.8]. Individuals having experienced a high VCM exposure and displaying a XRCC1 Gln-Gln genotype had a highest risk of p53 overexpression among those having different combinations of VCM exposure and XRCC1 genotypes (OR, 6.5; 95% CI, 1.7-24.2). Interestingly, those subjects reflecting a CYP2E1 c2c2 genotype among the low VCM-exposure group demonstrated a greater risk of p53 overexpression (OR, 9.8; 95% CI, 1.2-81.6) as compared with those experiencing a low VCM exposure and CYP2E1 c1c1/c1c2 genotypes. Additional analysis revealed that individuals possessing more susceptible XRCC1 Gln-Gln, CYP2E1 c2c2, ALDH2 1-2/2-2, and non-null GSTT1 genotypes were more likely to reveal p53 overexpression. Our results suggest that susceptible XRCC1 and CYP2E1 genotypes may modulate the mutation of the p53 gene among VCM-exposed workers.
SDGs
Other Subjects
aldehyde dehydrogenase isoenzyme 2; cytochrome P450 2E1; gene product; glutathione transferase; polyvinylchloride; protein antibody; protein p53; protein p53 antibody; unclassified drug; x ray repair cross complementing group 1; adult; aged; article; cancer risk; cancer susceptibility; carcinogenesis; controlled study; DNA repair; enzyme linked immunosorbent assay; exon; gene mutation; gene overexpression; genetic analysis; genetic polymorphism; genetic susceptibility; genotype; high risk population; human; major clinical study; male; occupational exposure; polymerase chain reaction; priority journal; protein expression; risk factor; tumor suppressor gene; Age Factors; Alcohol Drinking; Aldehyde Dehydrogenase; Antibodies; Carcinogens; Cohort Studies; Cytochrome P-450 CYP2E1; DNA-Binding Proteins; Dose-Response Relationship, Drug; Gene Expression Regulation; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Male; Middle Aged; Occupational Exposure; Point Mutation; Polymorphism, Genetic; Polyvinyl Chloride; Prevalence; Smoking; Taiwan; Tumor Suppressor Protein p53; Vinyl Chloride
Type
journal article