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Cancer Epidemiology Biomarkers & Prevention Vol. 11, 1513-1530, December 2002
© 2002 American Association for Cancer Research

Review

Polymorphisms in DNA Repair Genes and Associations with Cancer Risk1

Ellen L. Goode, Cornelia M. Ulrich2 and John D. Potter

Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, and Department of Epidemiology, University of Washington, Seattle, Washington 98195

Common polymorphisms in DNA repair genes may alter protein function and an individual’s capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.




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 CarcinogenesisHome page
G. Matullo, A.M. Dunning, S. Guarrera, C. Baynes, S. Polidoro, S. Garte, H. Autrup, C. Malaveille, M. Peluso, L. Airoldi, et al.
DNA repair polymorphisms and cancer risk in non-smokers in a cohort study
Carcinogenesis, May 1, 2006; 27(5): 997 - 1007.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
A. S. Andrew, H. H. Nelson, K. T. Kelsey, J. H. Moore, A. C. Meng, D. P. Casella, T. D. Tosteson, A. R. Schned, and M. R. Karagas
Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility
Carcinogenesis, May 1, 2006; 27(5): 1030 - 1037.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
C. Y. Jung, J. E. Choi, J. M. Park, M. H. Chae, H.-G. Kang, K. M. Kim, S. J. Lee, W. K. Lee, S. Kam, S. I. Cha, et al.
Polymorphisms in the hMSH2 Gene and the Risk of Primary Lung Cancer.
Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 762 - 768.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
V. Moreno, F. Gemignani, S. Landi, L. Gioia-Patricola, A. Chabrier, I. Blanco, S. Gonzalez, E. Guino, G. Capella, F. Canzian, et al.
Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.
Clin. Cancer Res., April 1, 2006; 12(7): 2101 - 2108.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
J. W. Hill and M. K. Evans
Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase
Nucleic Acids Res., March 20, 2006; 34(5): 1620 - 1632.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
T. G. Natarajan, N. Ganesan, P. Carter-Nolan, C. A. Tucker, P. G. Shields, and L. L. Adams-Campbell
{gamma}-Radiation-Induced Chromosomal Mutagen Sensitivity Is Associated with Breast Cancer Risk in African-American Women: Caffeine Modulates the Outcome of Mutagen Sensitivity Assay.
Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 437 - 442.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
M. Garcia-Closas, N. Malats, F. X. Real, R. Welch, M. Kogevinas, N. Chatterjee, R. Pfeiffer, D. Silverman, M. Dosemeci, A. Tardon, et al.
Genetic variation in the nucleotide excision repair pathway and bladder cancer risk.
Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 536 - 542.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
B. F. Pachkowski, S. Winkel, Y. Kubota, J. A. Swenberg, R. C. Millikan, and J. Nakamura
XRCC1 Genotype and Breast Cancer: Functional Studies and Epidemiologic Data Show Interactions between XRCC1 Codon 280 His and Smoking.
Cancer Res., March 1, 2006; 66(5): 2860 - 2868.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
R. C. Millikan, A. Hummer, C. Begg, J. Player, A. R. de Cotret, S. Winkel, H. Mohrenweiser, N. Thomas, B. Armstrong, A. Kricker, et al.
Polymorphisms in nucleotide excision repair genes and risk of multiple primary melanoma: the Genes Environment and Melanoma Study
Carcinogenesis, March 1, 2006; 27(3): 610 - 618.
[Abstract] [Full Text] [PDF]

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 MutagenesisHome page
G. Iarmarcovai, I. Sari-Minodier, T. Orsiere, M. De Meo, P. Gallice, C. Bideau, D. Iniesta, J. Pompili, J.L. Berge-Lefranc, and A. Botta
A combined analysis of XRCC1, XRCC3, GSTM1 and GSTT1 polymorphisms and centromere content of micronuclei in welders
Mutagenesis, March 1, 2006; 21(2): 159 - 165.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
K. Ekstrom Smedby, C. M. Lindgren, H. Hjalgrim, K. Humphreys, C. Schollkopf, E. T. Chang, G. Roos, L. P. Ryder, K. I. Falk, J. Palmgren, et al.
Variation in DNA Repair Genes ERCC2, XRCC1, and XRCC3 and Risk of Follicular Lymphoma.
Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 258 - 265.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
W.-Y. Huang, S. I. Berndt, D. Kang, N. Chatterjee, S. J. Chanock, M. Yeager, R. Welch, R. S. Bresalier, J. L. Weissfeld, and R. B. Hayes
Nucleotide Excision Repair Gene Polymorphisms and Risk of Advanced Colorectal Adenoma: XPC Polymorphisms Modify Smoking-Related Risk.
Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 306 - 311.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
Y. Zhang, P. A. Newcomb, K. M. Egan, L. Titus-Ernstoff, S. Chanock, R. Welch, L. A. Brinton, J. Lissowska, A. Bardin-Mikolajczak, B. Peplonska, et al.
Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer.
Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 353 - 358.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
L. B. Travis, C. S. Rabkin, L. M. Brown, J. M. Allan, B. P. Alter, C. B. Ambrosone, C. B. Begg, N. Caporaso, S. Chanock, A. DeMichele, et al.
Cancer Survivorship--Genetic Susceptibility and Second Primary Cancers: Research Strategies and Recommendations
J Natl Cancer Inst, January 4, 2006; 98(1): 15 - 25.
[Abstract] [Full Text] [PDF]

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 Mol Cancer ResHome page
M. S. Attene-Ramos, E. D. Wagner, M. J. Plewa, and H. R. Gaskins
Evidence That Hydrogen Sulfide Is a Genotoxic Agent
Mol. Cancer Res., January 1, 2006; 4(1): 9 - 14.
[Abstract] [Full Text] [PDF]

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 BloodHome page
P. A. Mehta, T. A. Alonzo, R. B. Gerbing, J. S. Elliott, T. A. Wilke, R. J. Kennedy, J. A. Ross, J. P. Perentesis, B. J. Lange, and S. M. Davies
XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report
Blood, January 1, 2006; 107(1): 39 - 45.
[Abstract] [Full Text] [PDF]

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 Am J EpidemiolHome page
R. J. Hung, J. Hall, P. Brennan, and P. Boffetta
Genetic Polymorphisms in the Base Excision Repair Pathway and Cancer Risk: A HuGE Review
Am. J. Epidemiol., November 15, 2005; 162(10): 925 - 942.
[Abstract] [Full Text] [PDF]

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 JCOHome page
J. M. Chan, P. H. Gann, and E. L. Giovannucci
Role of Diet in Prostate Cancer Development and Progression
J. Clin. Oncol., November 10, 2005; 23(32): 8152 - 8160.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
J. Bigler, C. M. Ulrich, T. Kawashima, J. Whitton, and J. D. Potter
DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps
Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2501 - 2508.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
G. Matullo, S. Guarrera, C. Sacerdote, S. Polidoro, L. Davico, S. Gamberini, M. Karagas, G. Casetta, L. Rolle, A. Piazza, et al.
Polymorphisms/Haplotypes in DNA Repair Genes and Smoking: A Bladder Cancer Case-Control Study
Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2569 - 2578.
[Abstract] [Full Text] [PDF]

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 MutagenesisHome page
G. Iarmarcovai, I. Sari-Minodier, F. Chaspoul, C. Botta, M. De Meo, T. Orsiere, J.L. Berge-Lefranc, P. Gallice, and A. Botta
Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms
Mutagenesis, November 1, 2005; 20(6): 425 - 432.
[Abstract] [Full Text] [PDF]

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 Neuro OncolHome page
M. Wrensch, K. T. Kelsey, M. Liu, R. Miike, M. Moghadassi, J. D. Sison, K. Aldape, A. McMillan, J. Wiemels, and J. K. Wiencke
ERCC1 and ERCC2 polymorphisms and adult glioma
Neuro-oncol, October 1, 2005; 7(4): 495 - 507.
[Abstract] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
R. C. Millikan, J. S. Player, A. R. deCotret, C.-K. Tse, and T. Keku
Polymorphisms in DNA Repair Genes, Medical Exposure to Ionizing Radiation, and Breast Cancer Risk
Cancer Epidemiol. Biomarkers Prev., October 1, 2005; 14(10): 2326 - 2334.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
M. Majumder, N. Sikdar, R. R. Paul, and B. Roy
Increased Risk of Oral Leukoplakia and Cancer Among Mixed Tobacco Users Carrying XRCC1 Variant Haplotypes and Cancer Among Smokers Carrying Two Risk Genotypes: One on Each of Two Loci, GSTM3 and XRCC1 (Codon 280)
Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2106 - 2112.
[Abstract] [Full Text] [PDF]

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 MutagenesisHome page
H. Hoffmann, C. Isner, J. Hogel, and G. Speit
Genetic polymorphisms and the effect of cigarette smoking in the comet assay
Mutagenesis, September 1, 2005; 20(5): 359 - 364.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
A. G. Casson, Z. Zheng, S. C. Evans, P. J. Veugelers, G. A. Porter, and D. L. Guernsey
Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma
Carcinogenesis, September 1, 2005; 26(9): 1536 - 1541.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
A. Ewart-Toland, Q. Dai, Y.-T. Gao, H. Nagase, M. G. Dunlop, S. M. Farrington, R. A. Barnetson, H. Anton-Culver, D. Peel, A. Ziogas, et al.
Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types
Carcinogenesis, August 1, 2005; 26(8): 1368 - 1373.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
B. Kuschel, G. Chenevix-Trench, A. B. Spurdle, X. Chen, J. L. Hopper, G. G. Giles, M. McCredie, J. Chang-Claude, C. S. Gregory, N. E. Day, et al.
Common Polymorphisms in ERCC2 (Xeroderma pigmentosum D) are not Associated with Breast Cancer Risk
Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1828 - 1831.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
G. S. Palapattu, S. Sutcliffe, P. J. Bastian, E. A. Platz, A. M. De Marzo, W. B. Isaacs, and W. G. Nelson
Prostate carcinogenesis and inflammation: emerging insights
Carcinogenesis, July 1, 2005; 26(7): 1170 - 1181.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
J. Chang-Claude, O. Popanda, X.-L. Tan, S. Kropp, I. Helmbold, D. von Fournier, W. Haase, M. L. Sautter-Bihl, F. Wenz, P. Schmezer, et al.
Association between Polymorphisms in the DNA Repair Genes, XRCC1, APE1, and XPD and Acute Side Effects of Radiotherapy in Breast Cancer Patients
Clin. Cancer Res., July 1, 2005; 11(13): 4802 - 4809.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. Kyoizumi, Y. Kusunoki, T. Hayashi, M. Hakoda, J. B. Cologne, and K. Nakachi
Individual Variation of Somatic Gene Mutability in Relation to Cancer Susceptibility: Prospective Study on Erythrocyte Glycophorin A Gene Mutations of Atomic Bomb Survivors
Cancer Res., June 15, 2005; 65(12): 5462 - 5469.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
K.-M. Lee, J.-Y. Choi, C. Kang, C. P. Kang, S. K. Park, H. Cho, D.-Y. Cho, K.-Y. Yoo, D.-Y. Noh, S.-H. Ahn, et al.
Genetic Polymorphisms of Selected DNA Repair Genes, Estrogen and Progesterone Receptor Status, and Breast Cancer Risk
Clin. Cancer Res., June 15, 2005; 11(12): 4620 - 4626.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
S. Blankenburg, I. R. Konig, R. Moessner, P. Laspe, K.-M. Thoms, U. Krueger, S. G. Khan, G. Westphal, C. Berking, M. Volkenandt, et al.
Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study
Carcinogenesis, June 1, 2005; 26(6): 1085 - 1090.
[Abstract] [Full Text] [PDF]

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 JCOHome page
A. J. Alberg, M. V. Brock, and J. M. Samet
Epidemiology of Lung Cancer: Looking to the Future
J. Clin. Oncol., May 10, 2005; 23(14): 3175 - 3185.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
R. Brem and J. Hall
XRCC1 is required for DNA single-strand break repair in human cells
Nucleic Acids Res., May 2, 2005; 33(8): 2512 - 2520.
[Abstract] [Full Text] [PDF]


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