Journal Article

XPD polymorphisms: effects on DNA repair proficiency

Ruth M. Lunn, Kathy J. Helzlsouer, Ram Parshad, David M. Umbach, Emily L. Harris, Katherine K. Sanford and Douglas A. Bell

in Carcinogenesis

Volume 21, issue 4, pages 551-555
Published in print April 2000 | ISSN: 0143-3334
Published online April 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.4.551
XPD polymorphisms: effects on DNA repair proficiency

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XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA 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 aberrations were scored per 100 metaphase cells following incubation at 37°C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (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/Lys751 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 Lys751 (common) allele may alter the XPD protein product resulting in sub-optimal repair of X-ray-induced DNA damage.

Keywords: 95% CI, 95% confidence interval; CS, cockayne syndrome; NER, nucleotide excision repair; OR, odds ratio; TTD, trichothiodystrophy; XP, xeroderma pigmentosum.

Journal Article.  3619 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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