Carcinogenesis, Vol. 21, No. 5, 965-971,
May 2000
© 2000 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells
Department of Cancer Cell Biology and
1 Occupational Health Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115,
2 Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA 94143–0560, USA,
3 National Taiwan University, College of Public Health, Institute of Occupational Medicine and Industrial Hygiene, Taipei, Taiwan and
4 Department of Pathology,
5 Thoracic Surgery Unit, Department of Surgery, and
6 Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence–Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced 32P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR–RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were 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 were carriers of the 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 XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.
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D. J. Park, J. Stoehlmacher, W. Zhang, D. D. Tsao-Wei, S. Groshen, and H.-J. Lenz A Xeroderma Pigmentosum Group D Gene Polymorphism Predicts Clinical Outcome to Platinum-based Chemotherapy in Patients with Advanced Colorectal Cancer Cancer Res., December 1, 2001; 61(24): 8654 - 8658. [Abstract] [Full Text] [PDF]
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H. Seker, D. Butkiewicz, E. D. Bowman, M. Rusin, M. Hedayati, L. Grossman, and C. C. Harris Functional Significance of XPD Polymorphic Variants: Attenuated Apoptosis in Human Lymphoblastoid Cells with the XPD 312 Asp/Asp Genotype Cancer Res., October 1, 2001; 61(20): 7430 - 7434. [Abstract] [Full Text] [PDF]
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G. Matullo, D. Palli, M. Peluso, S. Guarrera, S. Carturan, E. Celentano, V. Krogh, A. Munnia, R. Tumino, S. Polidoro, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and 32P-DNA adducts in a sample of healthy subjects Carcinogenesis, September 1, 2001; 22(9): 1437 - 1445. [Abstract] [Full Text] [PDF]
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K. Hemminki, G. Xu, S. Angelini, E. Snellman, C. T. Jansen, B. Lambert, and S.-M. Hou XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ Carcinogenesis, August 1, 2001; 22(8): 1185 - 1188. [Abstract] [Full Text] [PDF]
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J. J. Hu, T. R. Smith, M. S. Miller, H. W. Mohrenweiser, A. Golden, and L.D. Case Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity Carcinogenesis, June 1, 2001; 22(6): 917 - 922. [Abstract] [Full Text] [PDF]
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E. J. Duell, R. C. Millikan, G. S. Pittman, S. Winkel, R. M. Lunn, C.-K. J. Tse, A. Eaton, H. W. Mohrenweiser, B. Newman, and D. A. Bell Polymorphisms in the DNA Repair Gene XRCC1 and Breast Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 2001; 10(3): 217 - 222. [Abstract] [Full Text]
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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. C. Stern, D. M. Umbach, C. H. van Gils, R. M. Lunn, and J. A. Taylor DNA Repair Gene XRCC1 Polymorphisms, Smoking, and Bladder Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2001; 10(2): 125 - 131. [Abstract] [Full Text]
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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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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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