Skip to main content

Advertisement

SpringerLink
Log in

VARS2 V552V variant as prognostic marker in patients with early breast cancer

  • Original paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The present study analyzed the polymorphisms of DNA repair genes and their impact on the survival of 240 patients with early breast cancer. The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and thirteen polymorphisms in 12 DNA repair genes were determined using the Sequenom Mass array system. Among the target polymorphisms, VARS2 rs2074511 and POLE rs5744857 were found to correlate with survival after curative surgery in a log-rank test. No difference was found in the clinical and tumor characteristics according to the genotypes of these two coding variants, except for a higher incidence of positive ER in patients with the GG genotype of POLE rs5744857 (P = 0.025). Meanwhile, a multivariate analysis showed that the GG genotype of VARS2 V552 V (rs2301717) was significantly associated with disease-free survival (DFS; HR = 0.298; P = 0.044) and marginally with distant DFS (DDFS; HR = 0.266; P = 0.077). In particular, the VARS2 rs2074511 polymorphism was only associated with survival in patients with triple negative (TN)-type breast cancer (P = 0.018 for DFS and 0.042 for DDFS, respectively). In conclusion, VARS2 V552V may be considered as a prognostic factor for survival in patients with early breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Trojan J, et al. Functional analysis of hMLH1 variants and HNPCC-related mutations using a human expression system. Gastroenterology. 2002;122(1):211–9.

    Article  PubMed  CAS  Google Scholar 

  2. Hutter P, Couturier A, Rey-Berthod C. Two common forms of the human MLH1 gene may be associated with functional differences. J Med Genet. 2000;37(10):776–81.

    Article  PubMed  CAS  Google Scholar 

  3. Shin A, et al. Genotype-phenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity. Asian Pac J Cancer Prev. 2008;9(3):501–5.

    PubMed  Google Scholar 

  4. Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11(12):1513–30.

    PubMed  CAS  Google Scholar 

  5. Li J, et al. Genetic polymorphisms in the DNA repair enzyme ERCC2 and breast tumour risk in a Chinese population. J Int Med Res. 2008;36(3):479–88.

    PubMed  CAS  Google Scholar 

  6. Pooley KA, et al. Common single-nucleotide polymorphisms in DNA double-strand break repair genes and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3482–9.

    Article  PubMed  CAS  Google Scholar 

  7. Poplawski T, et al. Polymorphisms of the DNA mismatch repair gene HMSH2 in breast cancer occurence and progression. Breast Cancer Res Treat. 2005;94(3):199–204.

    Article  PubMed  CAS  Google Scholar 

  8. Shu XO, et al. A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(12):1462–7.

    PubMed  CAS  Google Scholar 

  9. Yuan HY, et al. FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acids Res. 2006;34(Web Server issue):W635–41.

    Article  PubMed  CAS  Google Scholar 

  10. Rorbach J, et al. Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation. Nucleic Acids Res. 2008;36(9):3065–74.

    Article  PubMed  CAS  Google Scholar 

  11. Lee JW, et al. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006;443(7107):50–5.

    Article  PubMed  CAS  Google Scholar 

  12. Vogel CL, et al. First-line Herceptin monotherapy in metastatic breast cancer. Oncology. 2001;61(Suppl 2):37–42.

    Article  PubMed  CAS  Google Scholar 

  13. Nangle LA, Motta CM, Schimmel P. Global effects of mistranslation from an editing defect in mammalian cells. Chem Biol. 2006;13(10):1091–100.

    Article  PubMed  CAS  Google Scholar 

  14. Bacher JM, Schimmel P. An editing-defective aminoacyl-tRNA synthetase is mutagenic in aging bacteria via the SOS response. Proc Natl Acad Sci USA. 2007;104(6):1907–12.

    Article  PubMed  CAS  Google Scholar 

  15. Ropcke G, Moen CJ, Hart AA, Demant P. Effects of the MHC on hormonal induction of mammary tumors and function of hypophyseal isografts in the mouse. Immunogenetics. 1990;31(5–6):347–55.

    Article  PubMed  CAS  Google Scholar 

  16. Dux A, Demant P. MHC-controlled susceptibility to C3H-MTV-induced mouse mammary tumors is predominantly systemic rather than local. Int J Cancer. 1987;40(3):372–7.

    Article  PubMed  CAS  Google Scholar 

  17. van Kooij M, de Groot K, van Vugt H, Aten J, Snoek M. Genotype versus phenotype: conflicting results in mapping a lung tumor susceptibility locus to the G7c recombination interval in the mouse MHC class III region. Immunogenetics. 2001;53(8):656–61.

    Article  PubMed  Google Scholar 

  18. Malkki M, Gooley T, Horowitz M, Petersdorf EW. MHC class I, II, and III microsatellite marker matching and survival in unrelated donor hematopoietic cell transplantation. Tissue Antigens. 2007;69(Suppl 1):46–9.

    Article  PubMed  Google Scholar 

  19. Harney SM, et al. Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis. Rheumatology (Oxford). 2008;47(12):1761–7.

    Article  CAS  Google Scholar 

  20. Snoek M, Teuscher C, van Vugt H. Molecular analysis of the major MHC recombinational hot spot located within the G7c gene of the murine class III region that is involved in disease susceptibility. J Immunol. 1998;160(1):266–72.

    PubMed  CAS  Google Scholar 

  21. Fijneman RJ, Oomen LC, Snoek M, Demant PA. A susceptibility gene for alveolar lung tumors in the mouse maps between Hsp70.3 and G7 within the H2 complex. Immunogenetics. 1995;41(2-3):106–9.

    Article  PubMed  CAS  Google Scholar 

  22. Lanning D, Lafuse WP. The mouse p52 subunit of the transcription/DNA repair factor TFIIH is located in the class III region of the H2 complex: cloning and sequence polymorphism. Immunogenetics. 1999;49(6):498–504.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MEST) (No. 2009-0091573).

Author information

Authors and Affiliations

  1. Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, Korea

    Yee Soo Chae, Soo Jung Lee, Joon Ho Moon, Byung Woog Kang, Jong Gwang Kim & Sang Kyun Sohn

  2. Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Jin Hyang Jung & Ho Yong Park

  3. Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Ji Young Park

  4. Department of Radiology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Hye Jung Kim

  5. Nuclear Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Sang-Woo Lee

  6. Breast Cancer Center, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Yee Soo Chae, Jin Hyang Jung, Ho Yong Park, Ji Young Park, Hye Jung Kim & Sang-Woo Lee

Authors
  1. Yee Soo Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soo Jung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joon Ho Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byung Woog Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jong Gwang Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sang Kyun Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jin Hyang Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ho Yong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ji Young Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hye Jung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sang-Woo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ho Yong Park or Ji Young Park.

Additional information

Ho Yong Park and Ji Young Park contributed equally to this manuscript as the corresponding authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chae, Y.S., Lee, S.J., Moon, J.H. et al. VARS2 V552V variant as prognostic marker in patients with early breast cancer. Med Oncol 28, 1273–1280 (2011). https://doi.org/10.1007/s12032-010-9574-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9574-4

Keywords

Search

Navigation