The role of XRCC1, XRCC3 and PALB2 genes in the genesis of breast cancer

Cover Page

Cite item

Full Text

Abstract

Background: this study describes the contribution of XRCC1, XRCC3 and PALB2 genes in the genesis of sporadic forms of breast cancer in Belarus patients. Materials and Methods: this study included 169 patients with sporadic breast cancer and 185 healthy patients. The molecular genetic analysis was performed by RFLP and PAGE electrophoresis. Results: in this study we identified genotypes of high risk breast cancer patient’s for PALB2, XRCC1 and XRCC3 genes. We also discovered a statistically significant associations between the GG genotype for p.Q399R (XRCC1) and tumor grade, and between TT genotype for XRCC3 gene and the presence of metastases in the regional lymph nodes. The patients with TT genotype (p.T241M, XRCC3) showed the fivefold increase in the risk of local breast cancer recurrence. Conclusion: For the first time it was determined the prevalence of polymorphic variants of the DNA repair genes: p.Q399R (XRCC1), p.T241M (XRCC3), p.T1100T (PALB2) and p.Q559P (PALB2) for Belarus patients with the breast cancer. Analysis of SNPs in the DNA repair key genes may have clinical and prognostic significance during the formation of high risk patient’s groups developing the breast cancer.

About the authors

Viachaslau Nikolaevich Kipen

Scientific and Practical Center of the State Committee forensic examinations of Belarus

Email: slavakipen@rambler.ru
junior researcher, master of biological sciences

Sergey Borisovich Melnov

International Sakharov Environmental University

Email: sbmelnov@rambler.ru
doctor of biological sciences, professor

Raisa Mikhaylovna Smolyakova

Republican Scientific-Practical Center of Oncology and Medical Radiology

Email: smol60@mail.ru
doctor of biological sciences, professor, docent

References

  1. Мутовин Г. Р. (2010) Клиническая генетика. Геномика и протеомика наследственной патологии. М:. ГЭОТАР-Медиа.
  2. Статистика онкологических заболеваний в Республике Беларусь, под ред. О. Г. Суконко. 2014. 382 с.
  3. Bu T., Liu L., Sun Y. et al. (2014) XRCC1 Arg399Gln polymorphism confers risk of breast cancer in American population: a meta-analysis of 10846 cases and 11723. PLoS One. V. 9 (1): P. 28.
  4. Chen M. B., Li C., Wei M. X. et al. (2009) XRCC1 Arg399Gln, Arg194Trp and Arg280His polymorphisms in breast cancer risk: a meta-analysis. Mutagenesis. V. 24 (4): P. 331-339.
  5. He X. F., Wei W., Li J. L. et al. (2013) Association between the XRCC3 T241M polymorphism and risk of cancer: evidence from 157 case-control studies. Gene. V. 4: P. 523.
  6. Heil J., Gondos A., Rauch G. et al. (2012) Outcome analysis of patients with primary breast cancer initially treated at a certified academic breast unit. Breast. V. 21 (3): P. 303-308.
  7. Johanson H. C., Valentine H., Carol W. et al. (2009) DNA elution from buccal cells stored on Whatman FTA Classic Cards using a modifed methanol fxation method. Sturm BioTechniques. V.46: P. 309-311.
  8. Hussien Y. M., Gharib A. F., Awad A. F. et al. (2012) Impact of DNA repair genes polymorphism (XPD and XRCC1) on the risk of breast cancer in Egyptian female patients. Mol Biol Rep. V. 39 (2): P. 1895-1901.
  9. Kheirelseid E. A., Jumustafa H., Miller N. et al. (2011) Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics. Breast Cancer Res Treat. V. 126 (1): P. 131-140.
  10. Krupa R., Synomiec E., Pawlowska E. et al. (2009) Polymorphism of the homologous recombination repair genes RAD51 and XRCC3 in breast cancer. Exp Mol Pathol. V. 87 (1): P. 32-35.
  11. Lucci A., Hall C. S., Lodhi A. K. et al. (2012) Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. V. 13 (7): P. 688-695.
  12. Rodriguez S., Gaunt T. R., Day I. N. M. (2009) American Journal of Epidemiology Advance Access. doi: 10.1093/aje/kwn359/.
  13. Romanowicz-Makowska H., Smolarz B., Zadrozny M. et al. (2011) Single nucleotide polymorphisms in the homologous recombination repair genes and breast cancer risk in Polish women. Tohoku J Exp Med. V. 224 (3): P. 201-208.
  14. Silva S. N., Tomar M., Paulo C. et al. (2010) Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51. Cancer Epidemiol. V.34 (1): P. 85-92.
  15. Sy S. M. H., Huen M. S. Y., Chen J. J. (2009) PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci. V. 15: P. 7155-7160.
  16. Xia B., Sheng Q., Nakanishi K. et al. (2009) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Molecular Cell. P. 719-729.
  17. Zhang F., Ma J.L., Wu J.X. et al. (2009) PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Current Biology. V. 15: P. 524-529.
  18. Zipprich J., Terry M. B., Brandt-Rauf P. et al. (2010) XRCC1 polymorphisms and breast cancer risk from the New York Site of the Breast Cancer Family Registry: A family-based case-control study. J Carcinog. V.16 (9): P. 4.

Copyright (c) 2015 Kipen V.N., Melnov S.B., Smolyakova R.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies