Carcinogenesis, Vol. 22, No. 6, 917-922,
June 2001
© 2001 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity
1 Department of Cancer Biology and
2 Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157,
3 Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550 and
4 Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
Although several variants of DNA repair genes have been identified, their functional significance has not been determined. Using samples collected from 135 cancer-free women, this study evaluated whether amino acid substitution variants of DNA repair genes contribute to ionizing radiation (IR) susceptibility as measured by prolonged cell cycle G2 delay. PCR–restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes: X-ray repair cross complementing group 1 (XRCC1, exon 6, C/T, 194 Arg/Trp and exon 10, G/A, 399 Arg/Gln), XRCC group 3 (XRCC3, exon 7, C/T, 241 Thr/Met) and apurinic/apyrimidinic endonuclease 1 (APE1, exon 5, T/G, 148 Asp/Glu). Fluorescence-activated cell sorter (FACS) analysis was used to measure cell cycle delay. APE1 (exon 5) genotype was significantly associated with mitotic delay (P = 0.01), with the Glu/Glu genotype having prolonged delay compared with the other two genotypes. The mitotic delay index (mean ± SD) in women with the APE1 codon 148 Asp/Asp, Asp/Glu and Glu/Glu genotypes was 30.95 ± 10.15 (n = 49), 30.65 ± 10.4 (n = 60) and 39.56 ± 13.12 (n = 21), respectively. There was a significant interaction between family history (FH) and APE1 (exon 5) genotype (P = 0.007) as well as FH and XRCC1 (exon 10) genotype (P = 0.005) in mitotic delay. Lastly, prolonged cell cycle delay was significantly associated with number of variant alleles when APE1 Asp148Glu and XRCC1 Arg399Gln genotypes were evaluated in a four-level model (
2 for linear trend = 10.9; P = 0.001). These results suggest that amino acid substitution variants of XRCC1 and APE1 may contribute to IR hypersensitivity.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. A. Mateuca, M. Roelants, G. Iarmarcovai, P. V. Aka, L. Godderis, A. Tremp, S. Bonassi, M. Fenech, J.-L. Berge-Lefranc, and M. Kirsch-Volders hOGG1326, XRCC1399 and XRCC3241 polymorphisms influence micronucleus frequencies in human lymphocytes in vivo Mutagenesis, January 1, 2008; 23(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-Y. Huang, Y.-T. Gao, A. Rashid, L. C. Sakoda, J. Deng, M.-C. Shen, B.-S. Wang, T.-Q. Han, B.-H. Zhang, B. E. Chen, et al. Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China Carcinogenesis, January 1, 2008; 29(1): 100 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Breton, W. Zhou, M. L. Kile, E.A. Houseman, Q. Quamruzzaman, M. Rahman, G. Mahiuddin, and D. C. Christiani Susceptibility to arsenic-induced skin lesions from polymorphisms in base excision repair genes Carcinogenesis, July 1, 2007; 28(7): 1520 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Liu, W. Zhou, B. Y. Yeap, L. Su, J. C. Wain, J. M. Poneros, N. S. Nishioka, T. J. Lynch, and D. C. Christiani XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk Carcinogenesis, June 1, 2007; 28(6): 1254 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kuptsova, K. J. Kopecky, J. Godwin, J. Anderson, A. Hoque, C. L. Willman, M. L. Slovak, and C. B. Ambrosone Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials Blood, May 1, 2007; 109(9): 3936 - 3944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vodicka, R. Stetina, V. Polakova, E. Tulupova, A. Naccarati, L. Vodickova, R. Kumar, M. Hanova, B. Pardini, J. Slyskova, et al. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects Carcinogenesis, March 1, 2007; 28(3): 657 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Berndt, W.-Y. Huang, M. D. Fallin, K. J. Helzlsouer, E. A. Platz, J. L. Weissfeld, T. R. Church, R. Welch, S. J. Chanock, and R. B. Hayes Genetic Variation in Base Excision Repair Genes and the Prevalence of Advanced Colorectal Adenoma Cancer Res., February 1, 2007; 67(3): 1395 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Kaufmann, L. Filatov, S. E. Oglesbee, D. A. Simpson, M. A. Lotano, H. D. McKeen, L. R. Sawyer, D. T. Moore, R. C. Millikan, M. Cordeiro-Stone, et al. Radiation clastogenesis and cell cycle checkpoint function as functional markers of breast cancer risk Carcinogenesis, December 1, 2006; 27(12): 2519 - 2527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Varga, J. Hoegel, C. Maier, S. Jainta, M. Hoehne, B. Patino-Garcia, I. Michel, U. Schwarz-Boeger, M. Kiechle, R. Kreienberg, et al. On the difference of micronucleus frequencies in peripheral blood lymphocytes between breast cancer patients and controls Mutagenesis, September 1, 2006; 21(5): 313 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ye, R. Kumar, G. Bacova, J. Lagergren, K. Hemminki, and O. Nyren The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden Carcinogenesis, September 1, 2006; 27(9): 1835 - 1841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Li, Z. Liu, L.-E Wang, S. S. Strom, J. E. Lee, J. E. Gershenwald, M. I. Ross, P. F. Mansfield, J. N. Cormier, V. G. Prieto, et al. Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma Carcinogenesis, September 1, 2006; 27(9): 1894 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lam, S.-Y. Park, C.-H. Leung, and Y.-C. Cheng Apurinic/Apyrimidinic Endonuclease-1 Protein Level Is Associated with the Cytotoxicity of L-Configuration Deoxycytidine Analogs (Troxacitabine and beta-L-2',3'-Dideoxy-2',3'-didehydro-5-fluorocytidine) but Not D-Configuration Deoxycytidine Analogs (Gemcitabine and beta-D-Arabinofuranosylcytosine) Mol. Pharmacol., May 1, 2006; 69(5): 1607 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Z. Zhang, J. Wan, X. Jin, T. Jin, H. Shen, D. Lu, and Z. Xia Genetic Polymorphisms in XRCC1, APE1, ADPRT, XRCC2, and XRCC3 and Risk of Chronic Benzene Poisoning in a Chinese Occupational Population Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2614 - 2619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Sak, P. Harnden, C. F. Johnston, A. B. Paul, and A. E. Kiltie APE1 and XRCC1 Protein Expression Levels Predict Cancer-Specific Survival Following Radical Radiotherapy in Bladder Cancer Clin. Cancer Res., September 1, 2005; 11(17): 6205 - 6211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Huang, A. F. Olshan, S. M. Schwartz, S. I. Berndt, C. Chen, V. Llaca, S. J. Chanock, J. F. Fraumeni Jr., and R. B. Hayes Selected Genetic Polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and Risk of Head and Neck Cancer: A Pooled Analysis Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1747 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Hu, H. Ma, F. Chen, Q. Wei, and H. Shen XRCC1 Polymorphisms and Cancer Risk: A Meta-analysis of 38 Case-Control Studies Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1810 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Sadetzki, P. Flint-Richter, S. Starinsky, I. Novikov, Y. Lerman, B. Goldman, and E. Friedman Genotyping of Patients with Sporadic and Radiation-Associated Meningiomas Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 969 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shen, M. D. Gammon, M. B. Terry, L. Wang, Q. Wang, F. Zhang, S. L. Teitelbaum, S. M. Eng, S. K. Sagiv, M. M. Gaudet, et al. Polymorphisms in XRCC1 Modify the Association between Polycyclic Aromatic Hydrocarbon-DNA Adducts, Cigarette Smoking, Dietary Antioxidants, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 336 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ito, K. Matsuo, N. Hamajima, T. Mitsudomi, T. Sugiura, T. Saito, T. Yasue, K.-M. Lee, D. Kang, K.-Y. Yoo, et al. Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk Carcinogenesis, August 1, 2004; 25(8): 1395 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Han, G. A. Colditz, L. D. Samson, and D. J. Hunter Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk Cancer Res., May 1, 2004; 64(9): 3009 - 3013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Han, S. E. Hankinson, S. M. Zhang, I. De Vivo, and D. J. Hunter Interaction between Genetic Variations in DNA Repair Genes and Plasma Folate on Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 520 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Figueiredo, J. A. Knight, L. Briollais, I. L. Andrulis, and H. Ozcelik Polymorphisms XRCC1-R399Q and XRCC3-T241M and the Risk of Breast Cancer at the Ontario Site of the Breast Cancer Family Registry Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 583 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Han, S. E. Hankinson, H. Ranu, I. De Vivo, and D. J. Hunter Polymorphisms in DNA double-strand break repair genes and breast cancer risk in the Nurses' Health Study Carcinogenesis, February 1, 2004; 25(2): 189 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
N. Moullan, D. G. Cox, S. Angele, P. Romestaing, J.-P. Gerard, and J. Hall Polymorphisms in the DNA Repair Gene XRCC1, Breast Cancer Risk, and Response to Radiotherapy Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1168 - 1174. [Abstract] [Full Text]
|
|
|
|
|
|
S. Freitas, D. H. Moore, H. Michael, and M. R. Kelley Studies of Apurinic/Apyrimidinic Endonuclease/ref-1 Expression in Epithelial Ovarian Cancer: Correlations with Tumor Progression and Platinum Resistance Clin. Cancer Res., October 15, 2003; 9(13): 4689 - 4694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Smith, M. S. Miller, K. K. Lohman, L.D. Case, and J. J. Hu DNA damage and breast cancer risk Carcinogenesis, May 1, 2003; 24(5): 883 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Taverna, H.-s. Hwang, J. E. Schupp, T. Radivoyevitch, N. N. Session, G. Reddy, D. A. Zarling, and T. J. Kinsella Inhibition of Base Excision Repair Potentiates Iododeoxyuridine-induced Cytotoxicity and Radiosensitization Cancer Res., February 15, 2003; 63(4): 838 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Goode, C. M. Ulrich, and J. D. Potter Polymorphisms in DNA Repair Genes and Associations with Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1513 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 C. Vens, E. Dahmen-Mooren, M. Verwijs-Janssen, W. Blyweert, L. Graversen, H. Bartelink, and A. C. Begg The role of DNA polymerase {beta} in determining sensitivity to ionizing radiation in human tumor cells Nucleic Acids Res., July 1, 2002; 30(13): 2995 - 3004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Taylor, A. Thistlethwaite, and K. W. Caldecott Central Role for the XRCC1 BRCT I Domain in Mammalian DNA Single-Strand Break Repair Mol. Cell. Biol., April 15, 2002; 22(8): 2556 - 2563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Smith and Y. R. Seo p53 regulation of DNA excision repair pathways Mutagenesis, March 1, 2002; 17(2): 149 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Nelson, K. T. Kelsey, L. A. Mott, and M. R. Karagas The XRCC1 Arg399Gln Polymorphism, Sunburn, and Non-melanoma Skin Cancer: Evidence of Gene-Environment Interaction Cancer Res., January 1, 2002; 62(1): 152 - 155. [Abstract] [Full Text] [PDF]
|
|