XPD polymorphisms: effects on DNA repair proficiency

XPD codes for a DNA helicase involved in transcription and nucleotide excis ion repair. Rare XPD mutations diminish nucleotide excision repair resultin g in hypersensitivity to UV light and increased risk of skin cancer. Severa l polymorphisms in this gene have been identified but their impact on DNA r epair is not known. We compared XPD genotypes at codons 312 and 751 with DN A repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP, DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberration s were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals wi th the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aber rations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys75 1 genotype increased the risk of sub-optimal DNA repair (odds ratio 7.2, 95 % confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys 751 (common) allele may alter the XPD protein product resulting in suboptim al repair of X-ray -induced DNA damage.