Carcinogenesis, Vol. 21, No. 4, 551-555,
April 2000
© 2000 Oxford University Press
Accelerated Papers |
XPD polymorphisms: effects on DNA repair proficiency
1 Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, MD C3-03, PO Box 12233, Research Triangle Park, NC 27709,
2 Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD,
3 Department of Pathology, Howard University College of Medicine, Washington, DC,
4 Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC and
6 Laboratory of Cellular and Molecular Biology, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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.
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D. Butkiewicz, M. Rusin, L. Enewold, P. G. Shields, M. Chorazy, and C. C. Harris Genetic polymorphisms in DNA repair genes and risk of lung cancer Carcinogenesis, April 1, 2001; 22(4): 593 - 597. [Abstract] [Full Text] [PDF]
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D. Tomescu, G. Kavanagh, T. Ha, H. Campbell, and D. W. Melton Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma Carcinogenesis, March 1, 2001; 22(3): 403 - 408. [Abstract] [Full Text] [PDF]
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M. R. Spitz, X. Wu, Y. Wang, L.-E Wang, S. Shete, C. I. Amos, Z. Guo, L. Lei, H. Mohrenweiser, and Q. Wei Modulation of Nucleotide Excision Repair Capacity by XPD Polymorphisms in Lung Cancer Patients Cancer Res., February 1, 2001; 61(4): 1354 - 1357. [Abstract] [Full Text]
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 A. R. Lehmann The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases Genes & Dev., January 1, 2001; 15(1): 15 - 23. [Full Text]
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E. M. Sturgis, R. Zheng, L. Li, E. J. Castillo, S. A. Eicher, M. Chen, S. S. Strom, M. R. Spitz, and Q. Wei XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis Carcinogenesis, December 1, 2000; 21(12): 2219 - 2223. [Abstract] [Full Text] [PDF]
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B. N. Ford, C. C. Ruttan, V. L. Kyle, M. E. Brackley, and B. W. Glickman Identification of single nucleotide polymorphisms in human DNA repair genes Carcinogenesis, November 1, 2000; 21(11): 1977 - 1981. [Abstract] [Full Text] [PDF]
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 M. Z. Hadi, M. A. Coleman, K. Fidelis, H. W. Mohrenweiser, and D. M. Wilson III Functional characterization of Ape1 variants identified in the human population Nucleic Acids Res., October 15, 2000; 28(20): 3871 - 3879. [Abstract] [Full Text] [PDF]
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