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Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study

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Abstract

Genetic variation in DNA repair genes can alter an individual’s capacity to repair damaged DNA and influence the risk of cancer. We tested seven polymorphisms in DNA repair genes XRCC1, ERCC2, XRCC3, XRCC2, EXOI and TP53 for a possible association with breast cancer risk in a sample of 672 case and 672 control Russian women. An association was observed for allele A of the polymorphism XRCC1 (R399Q) rs25487 (co-dominant model AA vs. GG: OR 1.76, P = 0.003; additive model OR 1.28, P = 0.005; dominant model: OR 1.29, P = 0.03; recessive model OR 1.63, P = 0.008). Allele T of the polymorphism ERCC2 (D312N) rs1799793 was also associated with breast cancer risk (co-dominant model TT vs. CC: OR 1.43, P = 0.04; additive model OR 1.21, P = 0.02; dominant model: OR 1.30, P = 0.02), but the association became insignificant after applying Bonferroni correction. No association with breast cancer was found for the remaining SNPs. In summary, our study provides evidence that polymorphisms in DNA repair genes may play a role in susceptibility to breast cancer in the population of ethnical Russians.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49. doi:10.3322/caac.20006.

    Article  PubMed  Google Scholar 

  2. Davydov MI, Aksel EM. Cancer statistics in Russia and CIS in 2012. Moscow: Russian Cancer Research Center Publishing Group; 2014.

    Google Scholar 

  3. Miller K. Estrogen and DNA damage: the silent source of breast cancer? J Natl Cancer Inst. 2003;95:100–2. doi:10.1093/jnci/95.2.100.

    Article  CAS  PubMed  Google Scholar 

  4. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer—epidemiology, risk factors, and genetics. BMJ. 2000;321:624–8. doi:10.1136/bmj.321.7261.624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mulware SJ. The mammary gland carcinogens: the role of metal compounds and organic solvents. Int J Breast Cancer. 2013;2013:640851. doi:10.1155/2013/640851.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Muniandy PA, Liu J, Majumdar A, Liu S, Seidman MM. DNA interstrand crosslink repair in mammalian cells: step by step. Crit Rev Biochem Mol Biol. 2010;45:23–49. doi:10.1155/2013/640851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomark Prev. 2002;11:1513–30.

    CAS  Google Scholar 

  8. Wood RD, Mitchell M, Lindahl T. Human DNA repair genes, 2005. Mutat Res. 2005;577:275–83. doi:10.1016/j.mrfmmm.2005.03.007.

    Article  CAS  PubMed  Google Scholar 

  9. Moses RE. DNA damage processing defects and disease. Annu Rev Genomics Hum Genet. 2001;2:41–68. doi:10.1146/annurev.genom.2.1.41.

    Article  CAS  PubMed  Google Scholar 

  10. 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;59:2557–61.

    CAS  PubMed  Google Scholar 

  11. Duell EJ, Wiencke JK, Cheng TJ, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000;21:965–71. doi:10.1093/carcin/21.5.965.

    Article  CAS  PubMed  Google Scholar 

  12. Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect. 2003;111:1843–50. doi:10.1289/txg.6632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matullo G, Palli D, Peluso M, et al. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis. 2001;22:1437–45. doi:10.1093/carcin/22.9.1437.

    Article  CAS  PubMed  Google Scholar 

  14. Vodicka P, Kumar R, Stetina R, et al. Genetic polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. Carcinogenesis. 2004;25:757–63. doi:10.1093/carcin/bgh064.

    Article  CAS  PubMed  Google Scholar 

  15. Rafii S, O’Regan P, Xinarianos G, et al. A potential role for the XRCC2 R188H polymorphic site in DNA-damage repair and breast cancer. Hum Mol Genet. 2002;11:1433–8. doi:10.1093/hmg/11.12.1433.

    Article  CAS  PubMed  Google Scholar 

  16. Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G. Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol. 1999;19:1092–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nebel A, Flachsbart F, Till A, et al. A functional EXO1 promoter variant is associated with prolonged life expectancy in centenarians. Mech Ageing Dev. 2009;130:691–9. doi:10.1016/j.mad.2009.08.004.

    Article  CAS  PubMed  Google Scholar 

  18. Sherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29:308–11. doi:10.1093/nar/29.1.308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Loizidou MA, Michael T, Neuhausen SL, et al. Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast Cancer Res Treat. 2008;112:575–9. doi:10.1007/s10549-007-9881-4.

    Article  CAS  PubMed  Google Scholar 

  20. Pachkowski BF, Winkel S, Kubota Y, Swenberg JA, Millikan RC, Nakamura J. XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. Cancer Res. 2006;66:2860–8. doi:10.1158/0008-5472.

    Article  CAS  PubMed  Google Scholar 

  21. Jelonek K, Gdowicz-Klosok A, Pietrowska M, et al. Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. J Appl Genet. 2010;51:343–52. doi:10.1007/BF03208865.

    Article  CAS  PubMed  Google Scholar 

  22. Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y. Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population. J Thorac Oncol. 2012;7:954–62. doi:10.1097/JTO.0b013e31824de30f.

    Article  CAS  PubMed  Google Scholar 

  23. Shu XO, Cai Q, Gao YT, Wen W, Jin F, Zheng W. A population-based case–control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomark Prev. 2003;12:1462–7.

    CAS  Google Scholar 

  24. Sangrajrang S, Schmezer P, Burkholder I, et al. Polymorphisms in three base excision repair genes and breast cancer risk in Thai women. Breast Cancer Res Treat. 2008;111:279–88. doi:10.1007/s10549-007-9773-7.

    Article  CAS  PubMed  Google Scholar 

  25. Hsu MS, Yu JC, Wang HW, et al. Synergistic effects of polymorphisms in DNA repair genes and endogenous estrogen exposure on female breast cancer risk. Ann Surg Oncol. 2010;17:760–71. doi:10.1245/s10434-009-0802-0.

    Article  Google Scholar 

  26. Kim SU, Park SK, Yoo KY, et al. XRCC1 genetic polymorphism and breast cancer risk. Pharmacogenetics. 2002;12:335–8.

    Article  CAS  PubMed  Google Scholar 

  27. Duell EJ, Millikan RC, Pittman GS, et al. Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomark Prev. 2001;10:217–22.

    CAS  Google Scholar 

  28. Debniak T, Scott RJ, Huzarski T, et al. XPD common variants and their association with melanoma and breast cancer risk. Breast Cancer Res Treat. 2006;98:209–15. doi:10.1007/s10549-005-9151-2.

    Article  CAS  PubMed  Google Scholar 

  29. Kuschel B, Chenevix-Trench G, Spurdle AB, et al. Common polymorphisms in ERCC2 (Xeroderma pigmentosum D) are not associated with breast cancer risk. Cancer Epidemiol Biomark Prev. 2005;14:1828–31. doi:10.1158/1055-9965.EPI-04-0807.

    Article  CAS  Google Scholar 

  30. Smith TR, Levine EA, Freimanis RI, et al. Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. 2008;29:2132–8. doi:10.1093/carcin/bgn193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mechanic LE, Millikan RC, Player J, et al. Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case–control study. Carcinogenesis. 2006;27:1377–85. doi:10.1093/carcin/bgi330.

    Article  CAS  PubMed  Google Scholar 

  32. Lee SA, Lee KM, Park WY, et al. Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer. Exp Mol Med. 2005;37:86–90. doi:10.1038/emm.2005.12.

    Article  CAS  PubMed  Google Scholar 

  33. Song B, Zhu JY, Liu J, et al. Association of gene polymorphisms in the DNA repair gene XPD with risk of non-Hodgkin’s lymphoma. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:97–100.

    CAS  PubMed  Google Scholar 

  34. Jakubowska A, Gronwald J, Menkiszak J, et al. BRCA1-associated breast and ovarian cancer risks in Poland: no association with commonly studied polymorphisms. Breast Cancer Res Treat. 2010;119:201–11. doi:10.1007/s10549-009-0390-5.

    Article  PubMed  Google Scholar 

  35. Forsti A, Angelini S, Festa F, et al. Single nucleotide polymorphisms in breast cancer. Oncol Rep. 2004;11:917–22.

    PubMed  Google Scholar 

  36. Kuschel B, Auranen A, McBride S, et al. Variants in DNA double-strand break repair genes and breast cancer susceptibility. Hum Mol Genet. 2002;11:1399–407. doi:10.1093/hmg/11.12.1399.

    Article  CAS  PubMed  Google Scholar 

  37. Sangrajrang S, Schmezer P, Burkholder I, et al. The XRCC3 Thr241Met polymorphism and breast cancer risk: a case–control study in a Thai population. Biomarkers. 2007;12:523–32. doi:10.1080/13547500701395602.

    Article  CAS  PubMed  Google Scholar 

  38. Millikan RC, Player JS, Decotret AR, Tse CK, Keku T. Polymorphisms in DNA repair genes, medical exposure to ionizing radiation, and breast cancer risk. Cancer Epidemiol Biomark Prev. 2005;14:2326–34. doi:10.1158/1055-9965.EPI-05-0186.

    Article  CAS  Google Scholar 

  39. Lee KM, Choi JY, Kang C, et al. Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res. 2005;11:4620–6. doi:10.1158/1078-0432.CCR-04-2534.

    Article  CAS  PubMed  Google Scholar 

  40. Luo KQ, Mu SQ, Wu ZX, Shi YN, Peng JC. Polymorphisms in DNA repair genes and risk of glioma and meningioma. Asian Pac J Cancer Prev. 2013;14:449–52. doi:10.7314/APJCP.2013.14.1.449.

    Article  PubMed  Google Scholar 

  41. Szymanowska A, Jassem E, Dziadziuszko R, et al. Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism. Lung Cancer. 2006;52:9–14. doi:10.1016/j.lungcan.2005.12.007.

    Article  PubMed  Google Scholar 

  42. Popanda O, Edler L, Waas P, et al. Elevated risk of squamous-cell carcinoma of the lung in heavy smokers carrying the variant alleles of the TP53 Arg72Pro and p21 Ser31Arg polymorphisms. Lung Cancer. 2007;55:25–34. doi:10.1016/j.lungcan.2006.09.006.

    Article  PubMed  Google Scholar 

  43. Onel KB, Huo D, Hastings D, Fryer-Biggs J, Crow MK, Onel K. Lack of association of the TP53 Arg72Pro SNP and the MDM2 SNP309 with systemic lupus erythematosus in Caucasian, African American, and Asian children and adults. Lupus. 2009;18:61–6. doi:10.1177/0961203308094558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Murata M, Tagawa M, Kimura H, Kakisawa K, Shirasawa H, Fujisawa T. Correlation of the mutation of p53 gene and the polymorphism at codon 72 in smoking-related non-small cell lung cancer patients. Int J Oncol. 1998;12:577–81. doi:10.3892/ijo.12.3.577.

    CAS  PubMed  Google Scholar 

  45. Zdzienicka MZ, van der Schans GP, Natarajan AT, Thompson LH, Neuteboom I, Simons JW. A Chinese hamster ovary cell mutant (EM-C11) with sensitivity to simple alkylating agents and a very high level of sister chromatid exchanges. Mutagenesis. 1992;7:265–9. doi:10.1093/mutage/7.4.265.

    Article  CAS  PubMed  Google Scholar 

  46. Thompson LH, Brookman KW, Jones NJ, Allen SA, Carrano AV. Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Mol Cell Biol. 1990;10:6160–71. doi:10.1128/MCB.10.12.6160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Masson M, Niedergang C, Schreiber V, Muller S, Menissier-de Murcia J, de Murcia G. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol. 1998;18:3563–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang Y, Spitz MR, Zhu Y, Dong Q, Shete S, Wu X. From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair. 2003;2:901–8. doi:10.1016/S1568-7864(03)00085-5.

    Article  CAS  PubMed  Google Scholar 

  49. Lei Y-C, Hwang S, Chang C-C, et al. Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers. Mutat Res. 2002;519:93–101. doi:10.1016/S1383-5718(02)00127-4.

    Article  CAS  PubMed  Google Scholar 

  50. 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;159:63–71. doi:10.1016/S0304-3835(00)00532-2.

    Article  CAS  PubMed  Google Scholar 

  51. Bu T, Liu L, Sun Y, et al. XRCC1 Arg399Gln polymorphism confers risk of breast cancer in American population: a meta-analysis of 10846 cases and 11723 controls. PLoS ONE. 2014;9:e86086. doi:10.1371/journal.pone.0086086.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Li H, Ha TC, Tai BC. XRCC1 gene polymorphisms and breast cancer risk in different populations: a meta-analysis. Breast. 2009;18:183–91. doi:10.1016/j.breast.2009.03.008.

    Article  CAS  PubMed  Google Scholar 

  53. Saadat M, Ansari-Lari M. Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures. Breast Cancer Res Treat. 2009;115:137–44. doi:10.1007/s10549-008-0051-0.

    Article  CAS  PubMed  Google Scholar 

  54. Huang Y, Li L, Yu L. XRCC1 Arg399Gln, Arg194Trp and Arg280His polymorphisms in breast cancer risk: a meta-analysis. Mutagenesis. 2009;24:331–9. doi:10.1093/mutage/gep013.

    Article  CAS  PubMed  Google Scholar 

  55. Wu K, Su D, Lin K, Luo J, Au WW. XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case–control studies. Asian Pac J Cancer Prev. 2011;12:2237–43.

    PubMed  Google Scholar 

  56. Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, et al. Challenges to effective cancer control in China, India, and Russia. Lancet Oncol. 2014;15:489–538. doi:10.1016/S1470-2045(14)70029-4.

    Article  PubMed  Google Scholar 

  57. Pakpong P, Wild O, Akimoto H. Air pollution import to and export from East Asia. Handb Environ Chem. 2004;4G:99–130. doi:10.1007/b94525.

    Google Scholar 

  58. Lehmann AR. The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes Dev. 2001;15:15–23. doi:10.1101/gad.859501.

    Article  CAS  PubMed  Google Scholar 

  59. Pabalan N, Francisco-Pabalan O, Sung L, Jarjanazi H, Ozcelik H. Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer. Breast Cancer Res Treat. 2010;124:531–41. doi:10.1007/s10549-010-0863-6.

    Article  CAS  PubMed  Google Scholar 

  60. Hou S-M, Fält S, Angelini S, et al. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis. 2002;23:599–603. doi:10.1093/carcin/23.4.599.

    Article  CAS  PubMed  Google Scholar 

  61. Wolfe KJ, Wickliffe JK, Hill CE, Paolini M, Ammenheuser MM, Abdel-Rahman SZ. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics. 2007;17:897–905. doi:10.1097/FPC.0b013e3280115e63.

    Article  CAS  PubMed  Google Scholar 

  62. Qiao Y, Spitz MR, Shen H, et al. Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes. Carcinogenesis. 2002;23:295–9. doi:10.1093/carcin/23.2.295.

    Article  CAS  PubMed  Google Scholar 

  63. Hemminki K, Xu G, Angelini S, et al. XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis. 2001;22:1185–8. doi:10.1093/carcin/22.8.1185.

    Article  CAS  PubMed  Google Scholar 

  64. Jiang Z, Li C, Xu Y, Cai S, Wang X. Associations between XPD polymorphisms and risk of breast cancer: a meta-analysis. Breast Cancer Res Treat. 2010;123:203–12. doi:10.1007/s10549-010-0751-0.

    Article  PubMed  Google Scholar 

  65. Yao L, Qiu L-X, Yu L, et al. The association between ERCC2 Asp312Asn polymorphism and breast cancer risk: a meta-analysis involving 22,766 subjects. Breast Cancer Res Treat. 2010;123:227–31. doi:10.1007/s10549-010-0754-x.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the Altai Branch of the Russian Blokhin Cancer Research Centre group for support during the collection of clinical data.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All the individuals enrolled in this study gave signed informed consent, and the study was approved by the local ethics committee. All clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki.

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Lavrentjeva, 8, 630090, Novosibirsk, Russia

    Alexandra S. Shadrina, Natalia A. Ermolenko, Uljana A. Boyarskikh & Maxim L. Filipenko

  2. Novosibirsk State University, Pirogova Street, 2, 630090, Novosibirsk, Russia

    Alexandra S. Shadrina, Uljana A. Boyarskikh & Maxim L. Filipenko

  3. Altai Branch of the Russian Blokhin Cancer Research Centre, Nikitina Street, 77, 656049, Barnaul, Russia

    Tatiana V. Sinkina, Alexandr F. Lazarev & Valentina D. Petrova

  4. Kazan Federal University, Kremlyovskaya street, 18, 420008, Kazan, Republic of Tatarstan, Russia

    Maxim L. Filipenko

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  1. Alexandra S. Shadrina
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Shadrina, A.S., Ermolenko, N.A., Boyarskikh, U.A. et al. Polymorphisms in DNA repair genes and breast cancer risk in Russian population: a case–control study. Clin Exp Med 16, 21–28 (2016). https://doi.org/10.1007/s10238-014-0329-y

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