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.
Mutant p53 protein and anti-p53 antibody in circulating blood can be detectedamong 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.
Wong
Ruey-Hong
RH
Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan 100.
Du
Chung-Li
CL
Wang
Jung-Der
JD
Chan
Chang-Chuan
CC
Luo
Jiin-Chyuan J
JC
Cheng
Tsun-Jen
TJ
D000367:Age Factors; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000906:Antibodies / Q000276:immunology*; D002273:Carcinogens / Q000009:adverse effects*; D015331:Cohort Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011143:Polyvinyl Chloride / Q000009:adverse effects*; D015995:Prevalence; D012907:Smoking; D013624:Taiwan / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology*; D014752:Vinyl Chloride / Q000009:adverse effects*; D000076105:X-ray Repair Cross Complementing Protein 1
D000906:Antibodies; D002273:Carcinogens; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D011143:Polyvinyl Chloride; D019392:Cytochrome P-450 CYP2E1; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D014752:Vinyl Chloride