A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage.
We have recently demonstrated a significant dose-response relationship between vinyl chloride exposure and mutant p53 biomarkers in humans. The aim of this study was to examine a common polymorphism in the DNA repair gene XRCC1 as a potential biomarker of susceptibility modifying this relationship, consistent with the known mechanism of production of p53 mutations via vinyl chloride-induced etheno-DNA adducts, which are repaired by XRCC1. A cohort of 211 French vinyl chloride workers were genotyped for the XRCC1 codon 399 polymorphism (CGG>CAG; Arg>Gln). Among the homozygous Arg-Arg individuals, 34% were biomarker positive compared with 47% in the heterozygous Arg-Gln individuals (adjusted odds ratio 1.73, 95% CI0.93-3.22) and 66% in the homozygous Gln-Gln individuals (adjusted odds ratio 3.95, 95% CI 1.68-9.28), with a significant trend for increasing Gln allele dosage (p=0.002). These preliminary results suggest that a common polymorphism in a DNA repair gene can be an important biomarker of susceptibility for chemically induced genetic damage.
Li
Yongliang
Y
Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Marion
Marie-Jeanne
MJ
Rundle
Andrew
A
Brandt-Rauf
Paul W
PW
D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D014752:Vinyl Chloride / Q000506:poisoning*; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D019392:Cytochrome P-450 CYP2E1; D014752:Vinyl Chloride