© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 11, 874-897,
June 7, 2000
© 2000 Oxford University Press
REVIEW |
Markers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review
Affiliations of authors: M. Berwick, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; P. Vineis, Unit of Cancer Epidemiology, University of Torino, and Ospedale S. Giovanni Battista, Torino, Italy.
Correspondence to: Marianne Berwick, Ph.D., Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 588, New York, NY 10021 (e-mail: berwickm{at}mskcc.org).
DNA repair is a system of defenses designed to protect the integrity of the genome. Deficiencies in this system likely lead to the development of cancer. The epidemiology of DNA repair capacity and of its effect on cancer susceptibility in humans is, therefore, an important area of investigation. We have summarized all of the published epidemiologic studies on DNA repair in human cancer through 1998 (n = 64) that addressed the association of cancer susceptibility with a putative defect in DNA repair capacity. We have considered study design, subject characteristics, potential biases, confounding variables, and sources of technical variability. Assays of DNA repair capacity used, to date, can be broadly grouped into five categories: 1) tests based on DNA damage induced with chemicals or physical agents, such as the mutagen sensitivity assay, the G2-radiation assay, induced micronuclei, and the Comet assay; 2) indirect tests of DNA repair, such as unscheduled DNA synthesis; 3) tests based on more direct measures of repair kinetics, such as the host cell reactivation assay; 4) measures of genetic variation associated with DNA repair; and 5) combinations of more than one category of assay. The use of such tests in human populations yielded positive and consistent associations between DNA repair capacity and cancer occurrence (with odds ratios in the range of 1.4–75.3, with the majority of values between 2 and 10). However, the studies that we have reviewed have limitations, including small sample size, "convenience" controls, the use of cells different from the target organ, and the use of mutagens that do not occur in the natural environment. The evolving ability to study polymorphisms in DNA repair genes may contribute to new understandings about the mechanisms of DNA repair and the way in which DNA repair capacity affects the development of cancer.
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 M. B. Schabath, H. B. Grossman, G. L. Delclos, L. M. Hernandez, R. S. Day, B. R. Davis, S. P. Lerner, M. R. Spitz, and X. Wu Dietary Carotenoids and Genetic Instability Modify Bladder Cancer Risk J. Nutr., December 1, 2004; 134(12): 3362 - 3369. [Abstract] [Full Text] [PDF]
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M. S. Marin, M. F. Lopez-Cima, L. Garcia-Castro, T. Pascual, M. G. Marron, and A. Tardon Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1788 - 1793. [Abstract] [Full Text] [PDF]
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S. Rollinson, J. M. Allan, G. R. Law, P. L. Roddam, M. T. Smith, C. Skibola, A. G. Smith, M. S. Forrest, K. Sibley, R. Higuchi, et al. High-Throughput Association Testing on DNA Pools to Identify Genetic Variants that Confer Susceptibility to Acute Myeloid Leukemia Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 795 - 800. [Abstract] [Full Text] [PDF]
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S. Sanyal, F. Festa, S. Sakano, Z. Zhang, G. Steineck, U. Norming, H. Wijkstrom, P. Larsson, R. Kumar, and K. Hemminki Polymorphisms in DNA repair and metabolic genes in bladder cancer Carcinogenesis, May 1, 2004; 25(5): 729 - 734. [Abstract] [Full Text] [PDF]
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 H. W. Mohrenweiser Genetic Variation and Exposure Related Risk Estimation: Will Toxicology Enter a New Era? DNA Repair and Cancer as a Paradigm Toxicol Pathol, January 1, 2004; 32(1_suppl): 136 - 145. [Abstract] [PDF]
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J. Han, S. E. Hankinson, I. De Vivo, D. Spiegelman, R. M. Tamimi, H. W. Mohrenweiser, G. A. Colditz, and D. J. Hunter A Prospective Study of XRCC1 Haplotypes and Their Interaction with Plasma Carotenoids on Breast Cancer Risk Cancer Res., December 1, 2003; 63(23): 8536 - 8541. [Abstract] [Full Text] [PDF]
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N. Caporaso The Molecular Epidemiology of Oxidative Damage to DNA and Cancer J Natl Cancer Inst, September 3, 2003; 95(17): 1263 - 1265. [Full Text] [PDF]
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T. Paz-Elizur, M. Krupsky, S. Blumenstein, D. Elinger, E. Schechtman, and Z. Livneh DNA Repair Activity for Oxidative Damage and Risk of Lung Cancer J Natl Cancer Inst, September 3, 2003; 95(17): 1312 - 1319. [Abstract] [Full Text] [PDF]
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M. R. Spitz, Q. Wei, Q. Dong, C. I. Amos, and X. Wu Genetic Susceptibility to Lung Cancer: The Role of DNA Damage and Repair Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 689 - 698. [Full Text] [PDF]
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G. Matullo, M. Peluso, S. Polidoro, S. Guarrera, A. Munnia, V. Krogh, G. Masala, F. Berrino, S. Panico, R. Tumino, et al. Combination of DNA Repair Gene Single Nucleotide Polymorphisms and Increased Levels of DNA Adducts in a Population-based Study Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 674 - 677. [Abstract] [Full Text] [PDF]
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M. B. Schabath, M. R. Spitz, H. B. Grossman, K. Zhang, C. P. Dinney, P.-J. Zheng, and X. Wu Genetic Instability in Bladder Cancer Assessed by the Comet Assay J Natl Cancer Inst, April 2, 2003; 95(7): 540 - 547. [Abstract] [Full Text] [PDF]
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W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani Polymorphisms in the DNA Repair Genes XRCC1 and ERCC2, Smoking, and Lung Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 359 - 365. [Abstract] [Full Text] [PDF]
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B. Faraglia, S. Y. Chen, M. D. Gammon, Y. Zhang, S. L. Teitelbaum, A. I. Neugut, H. Ahsan, G. C. Garbowski, H. Hibshoosh, D. Lin, et al. Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke Carcinogenesis, April 1, 2003; 24(4): 719 - 725. [Abstract] [Full Text] [PDF]
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F. Veglia, G. Matullo, and P. Vineis Bulky DNA Adducts and Risk of Cancer: A Meta-Analysis Cancer Epidemiol. Biomarkers Prev., February 1, 2003; 12(2): 157 - 160. [Abstract] [Full Text] [PDF]
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Y.-L. Zheng, C. A. Loffredo, Z. Yu, R. T. Jones, M. J. Krasna, A. J. Alberg, R. Yung, D. Perlmutter, L. Enewold, C. C. Harris, et al. Bleomycin-induced chromosome breaks as a risk marker for lung cancer: a case-control study with population and hospital controls Carcinogenesis, February 1, 2003; 24(2): 269 - 274. [Abstract] [Full Text] [PDF]
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C. H. van Gils, R. M. Bostick, M. C. Stern, and J. A. Taylor Differences in Base Excision Repair Capacity May Modulate the Effect of Dietary Antioxidant Intake on Prostate Cancer Risk: An Example of Polymorphisms in the XRCC1 Gene Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1279 - 1284. [Abstract] [Full Text] [PDF]
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A. Collins and V. Harrington Repair of oxidative DNA damage: assessing its contribution to cancer prevention Mutagenesis, November 1, 2002; 17(6): 489 - 493. [Abstract] [Full Text] [PDF]
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P. G. Shields Tobacco Smoking, Harm Reduction, and Biomarkers J Natl Cancer Inst, October 2, 2002; 94(19): 1435 - 1444. [Abstract] [Full Text] [PDF]
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M. C. Stern, L. R. Johnson, D. A. Bell, and J. A. Taylor XPD Codon 751 Polymorphism, Metabolism Genes, Smoking, and Bladder Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1004 - 1011. [Abstract] [Full Text] [PDF]
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H. W. Mohrenweiser, T. Xi, J. Vazquez-Matias, and I. M. Jones Identification of 127Amino Acid Substitution Variants in Screening 37 DNA Repair Genes in Humans Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1054 - 1064. [Abstract] [Full Text] [PDF]
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E. J. Duell, E. A. Holly, P. M. Bracci, J. K. Wiencke, and K. T. Kelsey A Population-based Study of the Arg399Gln Polymorphism in X-Ray Repair Cross- Complementing Group 1 (XRCC1) and Risk of Pancreatic Adenocarcinoma Cancer Res., August 15, 2002; 62(16): 4630 - 4636. [Abstract] [Full Text] [PDF]
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A. K. Nersesyan Re: {gamma}-Radiation Sensitivity and Risk of Glioma J Natl Cancer Inst, June 19, 2002; 94(12): 949 - 949. [Full Text] [PDF]
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M. T. Landi, A. Baccarelli, A. C. Pesatori, M. Hedayati, L. Grossman, M. A. Tucker, and R. E. Tarone RESPONSE: Re: DNA Repair, Dysplastic Nevi, and Sunlight Sensitivity in the Development of Cutaneous Malignant Melanoma J Natl Cancer Inst, May 15, 2002; 94(10): 773 - 774. [Full Text] [PDF]
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K. Hemminki, G. Xu, L. Kause, L. M. Koulu, C. Zhao, and C. T. Jansen Demonstration of UV-dimers in human skin DNA in situ 3 weeks after exposure Carcinogenesis, April 1, 2002; 23(4): 605 - 609. [Abstract] [Full Text] [PDF]
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P. Brennan Gene-environment interaction and aetiology of cancer: what does it mean and how can we measure it? Carcinogenesis, March 1, 2002; 23(3): 381 - 387. [Abstract] [Full Text] [PDF]
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R. Lopez de Mesa, A. Lopez de Cerain Salsamendi, L. S. Ariznabarreta, M. J. C. Abinzano, and A. Patino-Garcia Measurement and analysis of the chemotherapy-induced genetic instability in pediatric cancer patients Mutagenesis, March 1, 2002; 17(2): 171 - 175. [Abstract] [Full Text] [PDF]
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K. J. Dornfeld and T. S. Lawrence A Predisposition Supposition for Glioma J Natl Cancer Inst, October 17, 2001; 93(20): 1512 - 1513. [Full Text] [PDF]
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M. L. Bondy, L.-E. Wang, R. El-Zein, M. de Andrade, M. S. Selvan, J. M. Bruner, V. A. Levin, W. K. Alfred Yung, P. Adatto, and Q. Wei {gamma}-Radiation Sensitivity and Risk of Glioma J Natl Cancer Inst, October 17, 2001; 93(20): 1553 - 1557. [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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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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 D. C. Malins, N. L. Polissar, G. K. Ostrander, and M. A. Vinson Single 8-oxo-guanine and 8-oxo-adenine lesions induce marked changes in the backbone structure of a 25-base DNA strand PNAS, October 26, 2000; (2000) 230438797. [Abstract] [Full Text]
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K. Hemminki, G. Xu, and F. Le Curieux Re: Markers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review J Natl Cancer Inst, September 20, 2000; 92(18): 1536 - 1537. [Full Text] [PDF]
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