A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage

Abstract

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.

Keywords: :

• vinyl chloride
• mutations
• p53
• DNA repair