Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells

Polymorphisms in several DNA repair genes have recently been identified, bu t little is known about their phenotypic significance, To determine whether variation in DNA repair genes is related to host DNA damage, we studied th e association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 7 51) and two markers of DNA damage, sister chromatid exchange (SCE) frequenc ies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were dete rmined using a modified fluorescence-Giemsa method and polyphenol DNA adduc ts were determined using a P1-enhanced P-32-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP, Mean SCE frequencies am ong current smokers who were homozygous carriers of the 399Gln allele in XR CC1 mere greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who mere carriers of t he 399Gln allele than in younger subjects with the 399Arg/Arg genotype, The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic YRCC1 399Gln allele ma y be at greater risk for tobacco- and age-related DNA damage.