Genetic polymorphism in DNA base excision repair gene XRCC1among medical radiation workers

Harry Nugroho Eko Surniyantoro(1*), Yanti Lusiyanti(2), Wiwin Mailana(3), Devita Tetriana(4)

(1) Center for Technology of Safety and Radiation Metrology, National Nuclear Energy Agency of Indonesia Jl. Lebak Bulus Raya 49, Jakarta 12070, Indonesia
(2) Center for Technology of Safety and Radiation Metrology, National Nuclear Energy Agency of Indonesia Jl. Lebak Bulus Raya 49, Jakarta 12070, Indonesia
(3) Center for Technology of Safety and Radiation Metrology, National Nuclear Energy Agency of Indonesia Jl. Lebak Bulus Raya 49, Jakarta 12070, Indonesia
(4) Center for Technology of Safety and Radiation Metrology, National Nuclear Energy Agency of Indonesia Jl. Lebak Bulus Raya 49, Jakarta 12070, Indonesia
(*) Corresponding Author


X-rays repair cross-complementing group 1 (XRCC1) gene is one of the gene that plays an important role in base excision repair system (BER) and DNA repair both single and double strand breaks. Individuals with XRCC1 exon 10 (Arg399Gln) gene polymorphisms and carrying 399Gln allele variants (A allele) have a greater risk of DNA damage than their wildtype, 399Arg. The aim of this study was to examine the genotype frequencies of single nucleotide polymorphisms (SNPs) of XRCC1 exon 10 among medical radiation workers. This study involved 77 samples from several hospitals in Indonesia. Genotyping of XRCC1 exon 10 gene polymorphism was performed using PCR-RFLP. Individuals carryingA allele had lower frequency than that is carrying their wildtype of 399Arg (0.39 vs. 0.61). The results indicated that 39% of medical radiation workers had a risk of repair efficiency of DNA damage and might influence an individual's risk of cancer. Ionizing radiation induces many types of damage to DNA, requiring multiple repair pathways to restore genomics integrity. Other important genes/pathways, especially those for DNA double-strand break repair, might also play a role and should be further investigated. Furthermore, polymorphisms leading to inefficient DNA repair might also be associated with late reactions to radiotherapy.


DNA damage; XRCC1; genetic polymorphism; DNA repair; medical radiation workers

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1. UNSCEAR, Ionizing Radiation: Sources and Biological Effects, United Nations Scientific Committee on Effects of Atomic Radiation, New York, 1982.
2. Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci USA 2003; 100(24):13761-6.
3. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001; 411(6835):366-74.
4. Berwick M, Vineis P. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 2000; 92(11):874-97.
5. Friedberg EC. DNA damage and repair. Nature 2003; 421(6921):436-40.
6. Wood RD, Mitchell M, Sgouros J and Lindahl T. Human DNA repair genes. Science 2001; 291(5507):1284-9.
7. Hu Z, Ma H, Chen F, Wei Q, Shen H. XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case-control studies. Cancer Epidemiol Biomarkers Prev 2005;14(7):1810-8.
8. Schneider J, Classen V, Helmig S. XRCC1 polymorphism and lung cancer risk. Expert Rev Mol Diagn 2008; 8(6):761-80.
9. Norjmaa B, Tulgaa K, Saitoh T. Base excision repair pathway and polymorphisms of XRCC1 gene. J Mol Pathol Epidemiol 2016; 1:1-4.
10. Parsons JL, Dianov GL. Co-ordination of base excision repair and genome stability. DNA Repair 2013;12(5):326-33.
11. Audebert M, Salles B, Calsou P. Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. J Biol Chem 2004;279(53):55117-26.
12. Thompson LH, West MG. XRCC1 keeps DNA from getting stranded. Mutat Res 2000; 459(1):11-8.
13. Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 2001; 22(6):917-22.
14. Sterpone S, Cozzi R. Influence of XRCC1 genetic polymorphisms on ionizing radiation-induced DNA damage and repair. J Nucleic Acids 2010; 2010: 780369.
15. Ochiai H. Single-base pair genome editing in human cells by using site-specific endonucleases. Int J Mol Sci 2015; 16(9):21128-37.
16. Divine KK, Gilliland FD, Crowell RE, Stidley CA, Bocklage TJ, Cook DL, et al. The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat Res 2001; 461(4):273-8.
17. Duell EJ, Millikan RC, Pittman GS, Winkel S, Lunn RM, Tse CK, et al. Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev 2001;10(3):217-22.
18. Mateuca RA, Roelants M, Iarmarcovai G, Aka PV, Godderis L, Tremp A, et al. hOGG1(326), XRCC1(399) and XRCC3(241) polymorphisms influence micronucleus frequencies in human lyphocytes in vivo. Mutagenesis 2008; 23(1):35-41.
19. Weng H, Weng Z, Lu Y, Nakayama K, Maromoto K. Effects of cigarette smoking, XRCC1 genetic polymorphisms, and age on basal DNA damage in human blood mononuclear cells. Mutat Res 2009; 679(1-2):59-64.
20. Andreassi MG, Foffa I, Manfredi S, Botto N, Cioppa A, Picano E. Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists. Mutat Res 2009; 666(1-2):57-63.
21. Seibold P, Schmezer P, Behrens S, Michailidou K, Bolla MK, Wang Q, et al. A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients. BMC Cancer 2015;15:978.
22. Norjmaa B, Saitoh T, Kasamatsu T, Minato Y, Murakami H. XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphisms affect clinical features and prognosis of myelodysplastic syndromes. Kitakanto Med J 2015; 65(1):11-9.
23. Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 1999; 59(11):2557-61.
24. Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TD, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000; 21(5):965-71.
25. Abdel-Rahman SZ, El Zein RA. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett 2000; 159(1):63-71.
26. Lei YC, Hwang SJ, Chang CC, Kuo HW, Luo JC, Chang MJ, et al. Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers. Mutat Res 2002; 519(1-2):93-101.
27. Saadat M. Haplotype analysis of XRCC1 (at codons 194 and 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat 2010; 124(3):785-91.
28. Borrego-Soto G, Ortiz-López R, Rojas-Martínez A.Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer.Genet Mol Biol2015;38(4):420-32.
29. Dunne-Daly CF. Principles of radiotherapy and radiobiology. Semin Oncol Nurs 1999; 15(4):250-9.
30. BAPETEN. Regulation of Head of Bapeten 4/2013


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