XRCC1 codon 399 polymorphism (RS25487) in the Ukrainian population

  • Ya. M. Mishchuk
  • Ye. V. Kharkivska
  • S. V. Serha
  • S. Ye. Shkliar
  • V. B. Katrii
  • O. K. Koliada
  • O. E. Stakhovskyi
  • E. O. Stakhovskyi
  • Yu. V. Vitruk
  • A. A. Kononenko
  • S. V. Demydov
  • L. I. Ostapchenko
  • I. A. Kozeretska


Aim. To estimate the frequency of XRCC1 codon 399 polymorphic variants in bladder cancer patients and in a control group and define association of this polymorphism with a bladder cancer in Ukrainian patients. Methods. We determined the allele frequencies for 111 patients and 92 controls. Genotyping was performed by PCR-RELP method. Results. The distribution of genotypes in control group was: Arg/Arg – 48 % (n=44), Arg/Gln – 41.3 % (n=38), Gln/Gln – 10.7 % (n=10), whereas in group of patients with a bladder cancer the following distribution was observed: Arg/Arg – 56.8 % (n=63), Arg/Gln – 27.9 % (n=31), Gln/Gln – 15.3 % (n=17). Genotype distribution in control group was within Hardy-Weinberg equilibrium (χ2=59.7, p<0.0001), whereas in patient group it was not (χ2=0.172, p=0.678). No significant association was observed between the XRCC1 Arg399Gln polymorphism and bladder cancer risk. Conclusions. It is indicated that XRCC1 codon 399 polymorphism may not contribute to bladder cancer susceptibility in the Ukrainian population.

Keywords: bladder cancer, polymorphism, XRCC1 gene, the cancer risk.


Knowles M.A., Hurst C.D. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat. Rev. Cancer. 2015. V. 15. P. 25-41. doi: 10.1038/nrc3817

Eble J.N., Sauter G., Epstein J.I., Sesterhenn I.A. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARCPress. 2004. P. 90.

Wang M., Wang X-J., Ma Y-F., Dai Z-M PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk. Ther. Clin. Risk Manag. 2015. V. 13. P. 237-245. doi: 10.2147/TCRM.S77089

Dudek A.M., Grotenhuis A.J., Vermeulen S.H., Kiemeney L.A., Verhaegh G.W. Urinary bladder cancer susceptibility markers. What do we know about functional mechanisms? Int. J. Mol. Sci. 2013. V. 14. P. 12346-12366. doi: 10.3390/ijms140612346

Pashos C.L., Botteman M.F., Laskin B.L., Redaelli A. Bladder cancer: epidemiology, diagnosis, and management. Cancer practice. 2002. V. 10. P. 311-322. doi: 10.1046/j.1523-5394.2002.106011.x

Stern M.C., Umbach D.M., vanGils C.H., Lunn R.M., Taylor J.A. DNA rapair gene XRCC1 polymorphisms, smoking and bladder cancer risk. Cancer Epidemiology, Biomarkers&Prevention. 2001. V. 10. P. 125-131.

Caldecott K.W., McKeown C.K., Tucker J.D., Ljungquis S., Thompson L.H. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol. Cell. Biol. 1994. V. 14. P. 68-76. doi: 10.1128/MCB.14.1.68

Mao Y., Xu X., Lin Y. Quantitative assessment of the associations between XRCC1 polymorphisms and bladder cancer risk. World. J. Surg. Oncol. 2013. V. 11. P. 58. doi: 10.1186/1477-7819-11-58

Wang M., Qin C., Zhu J., Yuan L., Fu G., Zhang Z., Yin C. Genetic variants of XRCC1, APE1 and ADPRT genes and risk of bladder cancer. DNA and Cell Biology. 2010. V. 29. P. 303-311. doi: 10.1089/dna.2009.0969

Ramaniuk V.P., Nikitchenko N.V., Savina N.V., Kuzhir T.D. , Rolevich A.I., Krasny S.A., Sushinsky V.E., Goncharova R.I. Polymorphism of DNA repair genes OGG1, XRCC1, XPD and ERCC6 in bladder cancer in Belarus. Biomarkers. 2014. V. 19. P. 509-516. doi: 10.3109/1354750X.2014.943291

Duell E.J., Wiencke J.K., Cheng T.J.Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000. V. 21. P. 965-971. doi: 10.1093/carcin/21.5.965

Yin M., Tan D., Wei Q. Genetic variants of the XRCC1 gene and susceptibility to esophageal cancer: a meta-analysis. Int. J. Clin. Exp. Med. 2009. V. 2. P. 26-35. doi: 10.1016/j.cancergencyto.2008.08.013

Arizono K. DNA Repair Gene hOGG1 Codon 326 and XRCC1 Codon 399 Polymorphisms and Bladder Cancer Risk in a Japanese Population. Jpn. J. Clin. Oncol. 2008. V. 38. P. 186-191. doi: 10.1093/jjco/hym176

Fontana L. DNA Repair Gene ERCC2, XPC, XRCC1, XRCC3 Polymorphisms and Associations with Bladder Cancer Risk in a French Cohort. Anticancer Research. 2008. V. 28. P. 1853-1856.

Shen M. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy. Cancer Epidemiol. Biomarkers Prev. 2003. V. 12. P. 1234-1240.

Kelsey K.T. A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer. Cancer Epidemiol. Biomarkers Prev. 2004. V. 13. P. 1337-1341.

Matullo G., Guarrera S., Carturan S. DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control study. Int. J. Cancer. 2001. V. 4. P. 562-567. doi: 10.1002/ijc.1228

Chiang C.-I., Huang Y.-L., Chen W.-J., Shiue H.-S., Huang C.-Y., Pu Y.-S., Lin Y.-C., Hsueh Y.-M. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma. Toxicology and Applied Pharmacology. 2014. V. 279. P. 373-379. doi: 10.1016/j.taap.2014.06.027

Zhuo W., Zhang L., Cai L., Zhu B., Chen Z. XRCC1 Arg399Gln polymorphism and bladder cancer risk: updated meta-analyses based on 5767 cases and 6919 controls. Exp. Biol. Med. 2013. V. 238. P. 66-76. doi: 10.1258/ebm.2012.012209

Dong L.M., Zhang X.Y., Teng H., Li M.S., Wang P. Meta-analysis demonstrates no association between XRCC1 Arg399Gln polymorphism and bladder cancer risk. Genet. Mol. Res. 2014. V. 13. P. 9976-9985. doi: 10.4238/2014.November.28.2

Liu N., Fei X., Shen Y., Shi W., Ma J. Correlation between XRCC 1 Arg399Gln genetic polymorphisms and susceptibility to bladder cancer: a meta-analysis. OncoTargets and Therapy. 2016. V. 9. P. 579-586. doi: 10.2147/OTT.S95658

Lao T., Gu W., Huang Q. A meta-analysis on XRCC1 R399Q and R194W polymorphisms, smoking and bladder cancer risk. Mutagenesis. 2008. V. 23. P. 523-532. doi: 10.1093/mutage/gen046

Li S., Peng Q., Chen Y., You J., Chen Z., Deng Y., Lao X., Wu H., Qin X., Zeng Z. DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk: a meta-analysis. PLoS ONE. 2013. V. 8. P. 1-14. doi: 10.1371/journal.pone.0073448

Denisov E.V., Cherdyntseva N.V., Litviakov N.V., Malinovskaya E.A., Babyshkina N.N., Belyavskaya V.A., Voevoda M.I. TP53 gene polymorphism in cancer risk: the modulating effect of ageing, ethnicity and TP53 somatic abnormalities. In: Cheng Y., editor. Tumor suppressor genes. Rijeka, Croatia: InTech. 2012. P. 79-110. Retrieved from: http://cdn.intechopen.com/pdfs/27564.pdf.

Dumont P., Leu J.I., Della Pietra A.C. 3rd, George D.L., Murphy M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003. V. 33. P. 357-365. doi: 10.1038/ng1093

Atramentova L.A., Utevskaia O.M. Statisticheskie metody v biologii. Gorlovka: Lіkhtar, 2008. 248 p. [in Russian]

Wei B., Zhou Y., Xu Z., Ruan J., Zhu M., Jin K., Zhou D., Hu Q., Wang Q., Wang Z., Yan Z. XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis. Prostate Cancer Prostatic Dis. 2011. V. 14. P. 225-231. doi: 10.1038/pcan.2011.26

Huang G.L., Guo H.Q., Yu C.Y., Liu X.Y., Li B.B., Wu J.J., He Z.W. XRCC1 polymorphisms and risk of nasopharyngeal carcinoma: a meta-analysis. AsianPac. J. CancerPrev. 2011. V. 12. P. 2329-2333.