Advertisement

Medical Oncology

, Volume 28, Issue 4, pp 1273–1280 | Cite as

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

  • Yee Soo Chae
  • Soo Jung Lee
  • Joon Ho Moon
  • Byung Woog Kang
  • Jong Gwang Kim
  • Sang Kyun Sohn
  • Jin Hyang Jung
  • Ho Yong Park
  • Ji Young Park
  • Hye Jung Kim
  • Sang-Woo Lee
Original paper

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.

Keywords

Early breast cancer DNA repair gene Polymorphism VARS2 rs2074511 Prognosis 

Notes

Acknowledgments

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

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Lee JW, et al. Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature. 2006;443(7107):50–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Vogel CL, et al. First-line Herceptin monotherapy in metastatic breast cancer. Oncology. 2001;61(Suppl 2):37–42.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Yee Soo Chae
    • 1
    • 6
  • Soo Jung Lee
    • 1
  • Joon Ho Moon
    • 1
  • Byung Woog Kang
    • 1
  • Jong Gwang Kim
    • 1
  • Sang Kyun Sohn
    • 1
  • Jin Hyang Jung
    • 2
    • 6
  • Ho Yong Park
    • 2
    • 6
  • Ji Young Park
    • 3
    • 6
  • Hye Jung Kim
    • 4
    • 6
  • Sang-Woo Lee
    • 5
    • 6
  1. 1.Department of Oncology/Hematology, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea
  2. 2.Department of Surgery, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea
  3. 3.Department of Pathology, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea
  4. 4.Department of Radiology, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea
  5. 5.Nuclear Medicine, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea
  6. 6.Breast Cancer Center, Kyungpook National University HospitalKyungpook National University School of MedicineDaeguKorea

Personalised recommendations