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

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2002-05, Vol.11 (5), p.475-482
• Main Authors: WONG, Ruey-Hong, DU, Chung-Li, WANG, Jung-Der, CHAN, Chang-Chuan, LUO, Jiin-Chyuan J, CHENG, Tsun-Jen
• Format: Article
• Language: English
• Subjects: Age Factors; Alcohol Drinking; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase, Mitochondrial; Antibodies - immunology; Biological and medical sciences; Carcinogens - adverse effects; Chemical compounds (mineral, organic); Chemical, physic and infectious diseases; Cohort Studies; Cytochrome P-450 CYP2E1 - genetics; DNA-Binding Proteins - genetics; Dose-Response Relationship, Drug; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation - genetics; Gene Frequency - genetics; Gene Frequency - immunology; Genetic Predisposition to Disease - genetics; Genotype; Glutathione Transferase - genetics; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Occupational Exposure - adverse effects; Occupational medicine; Point Mutation - genetics; Polymorphism, Genetic; Polyvinyl Chloride - adverse effects; Prevalence; Public health. Hygiene-occupational medicine; Smoking; Taiwan - epidemiology; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - immunology; Tumors; Vinyl Chloride - adverse effects; X-ray Repair Cross Complementing Protein 1
• ISSN: 1055-9965; 1538-7755

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.