Advertisement

Breast Cancer Research and Treatment

, Volume 119, Issue 3, pp 701–705 | Cite as

Association of interleukin-10 gene variation with breast cancer prognosis

  • Armin GergerEmail author
  • Wilfried Renner
  • Tanja Langsenlehner
  • Günter Hofmann
  • Gudrun Knechtel
  • Joanna Szkandera
  • Hellmut Samonigg
  • Peter Krippl
  • Uwe Langsenlehner
Epidemiology

Abstract

Genetic polymorphisms are responsible for inter-individual variation and diversity and have been recently considered as the main genetic elements involved in the development and progression of cancer. We examined associations between common germline genetic variants in 7 genes involved in folate metabolism, cell proliferation and apoptosis, prostaglandin synthesis, detoxification of compounds and inflammation, and disease-free survival among women diagnosed with invasive breast cancer. DNA from up to 432 women was genotyped for 8 polymorphisms. The genotypes of each polymorphism were tested for association with disease-free survival using univariate and multivariate Cox regression analysis. The model was adjusted for known breast cancer prognostic factors. The rare allele of the IL-10 592C>A polymorphism was significantly associated with reduced disease-free survival (P = 0.018, risk ratio of recurrence (RR) = 1.45, 95% confidence interval (CI) = 1.06–1.98), which was not attenuated after adjusting for age at diagnosis, tumor size, lymph node status, clinical stage, histological grade, estrogen receptor status, progesterone receptor status, and treatment modalities (P = 0.019, RR = 1.48, 95% CI = 1.066–2.044). No association was found between MTHFR 677C>T, TGFB1 29T>C, FASLG 844C>T, FAS 1377G>A, FAS 670A>G, PTGS2 8473T>C and SULT1A1 638G>A polymorphisms and disease-free survival. Our data suggest that the rare allele of IL-10 592C>A may be a potential prognostic marker in breast cancer for disease-free survival.

Keywords

Breast cancer Prognosis Polymorphism Interleukin 

References

  1. 1.
    Rannala B (2001) Finding genes influencing susceptibility to complex diseases in the post-genome era. Am J Pharmacogenomics 1(3):203–221. doi: 10.2165/00129785-200101030-00005 CrossRefPubMedGoogle Scholar
  2. 2.
    Weigelt B, Peterse JL, van‘t Veer LJ (2005) Breast cancer metastasis: markers and models. Nat Rev Cancer 5:591–602. doi: 10.1038/nrc1670 CrossRefPubMedGoogle Scholar
  3. 3.
    Parkin DM, Bray F, Ferlay J et al (2002) Global cancer statistics. CA Cancer J Clin 55:74–108. doi: 10.3322/canjclin.55.2.74 CrossRefGoogle Scholar
  4. 4.
    Hunter K (2005) The intersection of inheritance and metastasis: the role and implications of germline polymorphism in tumor dissemination. Cell Cycle 4(12):1719–1721PubMedGoogle Scholar
  5. 5.
    Hsieh SM, Lintell NA, Hunter KW (2007) Germline polymorphisms are potential metastasis risk and prognosis markers in breast cancer. Breast Dis 26:157–162Google Scholar
  6. 6.
    Hunter K (2006) Breast host genetics influence tumour metastasis. Nat Rev Cancer 6(2):141–146. doi: 10.1038/nrc1803 CrossRefPubMedGoogle Scholar
  7. 7.
    Schneider BP, Wang M, Radovich M et al (2008) Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26(28):4672–4678. doi: 10.1200/JCO.2008.16.1612 CrossRefPubMedGoogle Scholar
  8. 8.
    Lenz HJ (2004) The use and development of germline polymorphisms in clinical oncology. J Clin Oncol 22(13):2519–2521. doi: 10.1200/JCO.2004.04.900 CrossRefPubMedGoogle Scholar
  9. 9.
    Hayes DF, Ethier S, Mippman ME (2006) New guidelines for reporting of tumor marker studies in breast cancer research and treatment: REMARK. Breast Cancer Res Treat 100:237–238. doi: 10.1007/s10549-006-9253-5 CrossRefPubMedGoogle Scholar
  10. 10.
    McShane LM, Altman DG, Sauerbrei W et al (2006) Reporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100:229–235. doi: 10.1007/s10549-006-9242-8 CrossRefPubMedGoogle Scholar
  11. 11.
    Langsenlehner U, Krippl P, Renner W et al (2003) The common 677C>T gene polymorphism of methylenetetrahydrofolate reductase gene is not associated with breast cancer risk. Breast Cancer Res Treat 81(2):169–172. doi: 10.1023/A:1025752420309 CrossRefPubMedGoogle Scholar
  12. 12.
    Langsenlehner U, Krippl P, Renner W et al (2005) Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 90(2):113–115. doi: 10.1007/s10549-004-3607-7 CrossRefPubMedGoogle Scholar
  13. 13.
    Krippl P, Langsenlehner U, Renner W et al (2004) Re: polymorphisms of death pathway genes FAS and FASL in esophageal squamous-cell carcinoma. J Natl Cancer Inst 96(19):1478–1479PubMedCrossRefGoogle Scholar
  14. 14.
    Krippl P, Langsenlehner U, Renner W et al (2003) The L10P polymorphism of the transforming growth factor-beta 1 gene is not associated with breast cancer risk. Cancer Lett 201(2):181–184. doi: 10.1016/S0304-3835(03)00468-3 CrossRefPubMedGoogle Scholar
  15. 15.
    Langsenlehner U, Krippl P, Renner W et al (2004) Genetic variants of the sulfotransferase 1A1 and breast cancer risk. Breast Cancer Res Treat 87(1):19–22. doi: 10.1023/B:BREA.0000041574.90735.ea CrossRefPubMedGoogle Scholar
  16. 16.
    Langsenlehner U, Yazdani-Biuki B, Eder T et al (2006) The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk. Clin Cancer Res 12(4):1392–1394. doi: 10.1158/1078-0432.CCR-05-2055 CrossRefPubMedGoogle Scholar
  17. 17.
    Gerger A, Langsenlehner U, Renner W et al (2007) A multigenetic approach to predict breast cancer risk. Breast Cancer Res Treat 104(2):159–164. doi: 10.1007/s10549-006-9408-4 CrossRefPubMedGoogle Scholar
  18. 18.
    Mocellin S, Marincola F, Rossi CR et al (2004) The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle. Cytokine Growth Factor Rev 15:61–76. doi: 10.1016/j.cytogfr.2003.11.001 CrossRefPubMedGoogle Scholar
  19. 19.
    Fiorentino DF, Zlotnik A, Mosmann TR et al (1991) IL10 inhibits cytokine production by activated macrophages. J Immunol 147:3815–3822PubMedGoogle Scholar
  20. 20.
    Turner DM, Williams DM, Sankaran D et al (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8PubMedGoogle Scholar
  21. 21.
    Crawley E, Kay R, Sillibourne J et al (1999) Polymorphic haplotypes of the interleukin-10 5’ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 42:1101–1108. doi: 10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO;2-Y CrossRefPubMedGoogle Scholar
  22. 22.
    Lin MT, Storer B, Martin PJ et al (2003) Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med 349:2201–2210. doi: 10.1056/NEJMoa022060 CrossRefPubMedGoogle Scholar
  23. 23.
    Holler E, Roncarolo MG, Hintermeier-Knabe R et al (2000) Prognostic significance of increased IL10 production in patients prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 25:237–241. doi: 10.1038/sj.bmt.1702126 CrossRefPubMedGoogle Scholar
  24. 24.
    Balasubramanian SP, Azmy IA, Higham SE et al (2006) Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review. BMC Cancer 6:188. doi: 10.1186/1471-2407-6-188 CrossRefPubMedGoogle Scholar
  25. 25.
    Howell WM, Rose-Zerilli MJ (2006) Interleukin-10 polymorphisms, cancer susceptibility and prognosis. Fam Cancer 5(2):143–149. doi: 10.1007/s10689-005-0072-3 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Armin Gerger
    • 1
    Email author
  • Wilfried Renner
    • 2
  • Tanja Langsenlehner
    • 3
  • Günter Hofmann
    • 1
  • Gudrun Knechtel
    • 1
  • Joanna Szkandera
    • 1
  • Hellmut Samonigg
    • 1
  • Peter Krippl
    • 4
  • Uwe Langsenlehner
    • 5
  1. 1.Division of Oncology, Department of Internal MedicineMedical University Graz, AustriaGrazAustria
  2. 2.Clinical Institute of Medical and Laboratory DiagnosticsMedical University Graz, AustriaGrazAustria
  3. 3.Clinic of Therapeutic Radiology and OncologyMedical University Graz, AustriaGrazAustria
  4. 4.Department of Internal MedicineRegional Hospital of FuerstenfeldFuerstenfeldAustria
  5. 5.Internal Outpatient DepartmentSteiermaerkische GebietskrankenkasseGrazAustria

Personalised recommendations