Advertisement

Breast Cancer Research and Treatment

, Volume 127, Issue 2, pp 549–554 | Cite as

Genetic variants within miR-126 and miR-335 are not associated with breast cancer risk

  • Rongxi Yang
  • Michelle Dick
  • Frederik Marme
  • Andreas Schneeweiss
  • Anne Langheinz
  • Kari Hemminki
  • Christian Sutter
  • Peter Bugert
  • Barbara Wappenschmidt
  • Raymonda Varon
  • Sarah Schott
  • Bernhard H. F. Weber
  • Dieter Niederacher
  • Norbert Arnold
  • Alfons Meindl
  • Claus R. Bartram
  • Rita K. Schmutzler
  • Heiko Müller
  • Volker Arndt
  • Hermann Brenner
  • Christof Sohn
  • Barbara Burwinkel
Epidemiology

Abstract

MicroRNAs (miRNAs) are 20–22 nt non-coding RNAs which promote the degradation of target mRNAs or repression of the translation of mRNAs by sequence specific targeting. Many miRNAs are considered as oncogenes or tumor suppressors. MiR-126 and miR-335 play roles in the suppression of breast cancer metastasis by inhibiting tumor growth, proliferation, and cell invasion. The effects of SNPs within the two miRNAs are still unknown. In our study, we analyzed two SNPs, rs4636297 within miR-126 and rs41272366 within miR-335, in three study populations for a putative association with breast cancer risk. We compared the genotype and allele frequencies of rs4636297 and rs41272366 in 2854 cases versus 3188 controls of the three study populations independently and combined. None of the performed analyses showed statistically significant results. In conclusion, our data suggest that the two genetic variants within miR-126 and miR-335 are not associated with breast cancer risk.

Keywords

Breast cancer Polymorphism miRNA Genetic variants SNP 

Notes

Acknowledgments

This study was supported by the Dietmar-Hopp Foundation, the Helmholtz society and the German Cancer Research Center (DKFZ). The German breast cancer samples were collected within a project funded by the Deutsche Krebshilfe (Grant number: 107054). The VERDI study was supported by the Deutsche Krebshilfe (Grant number: M24/95/BRI). The ESTHER study was supported by a grant from the Baden-Württemberg Ministry of Science, Research, and Arts.

References

  1. 1.
    Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–71PubMedCrossRefGoogle Scholar
  2. 2.
    Zeng Y, Yi R, Cullen BR (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA 100:9779–9784PubMedCrossRefGoogle Scholar
  3. 3.
    Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63PubMedCrossRefGoogle Scholar
  4. 4.
    Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845PubMedCrossRefGoogle Scholar
  5. 5.
    Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003) Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113:25–36PubMedCrossRefGoogle Scholar
  6. 6.
    Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745–752PubMedCrossRefGoogle Scholar
  7. 7.
    Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI et al (2008) MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci USA 105:5166–5171PubMedCrossRefGoogle Scholar
  8. 8.
    Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT et al (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38:1060–1065PubMedCrossRefGoogle Scholar
  9. 9.
    Xiao C, Rajewsky K (2009) MicroRNA control in the immune system: basic principles. Cell 136:26–36PubMedCrossRefGoogle Scholar
  10. 10.
    Croce CM (2009) Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–714PubMedCrossRefGoogle Scholar
  11. 11.
    Khoshnaw SM, Green AR, Powe DG, Ellis IO (2009) MicroRNA involvement in the pathogenesis and management of breast cancer. J Clin Pathol 62:422–428PubMedCrossRefGoogle Scholar
  12. 12.
    Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647PubMedCrossRefGoogle Scholar
  13. 13.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833PubMedCrossRefGoogle Scholar
  14. 14.
    O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843PubMedCrossRefGoogle Scholar
  15. 15.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRefGoogle Scholar
  16. 16.
    Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39:673–677PubMedCrossRefGoogle Scholar
  17. 17.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866PubMedCrossRefGoogle Scholar
  18. 18.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838PubMedCrossRefGoogle Scholar
  19. 19.
    Key TJ, Verkasalo PK, Banks E (2001) Epidemiology of breast cancer. Lancet Oncol 2:133–140PubMedCrossRefGoogle Scholar
  20. 20.
    Belkora J, Moore DH, Hutton DW (2009) Assessing risk communication in breast cancer: are continuous measures of patient knowledge better than categorical? Patient Educ Couns 76:106–112PubMedCrossRefGoogle Scholar
  21. 21.
    Ponder BA (2001) Cancer genetics. Nature 411:336–341PubMedCrossRefGoogle Scholar
  22. 22.
    Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36PubMedCrossRefGoogle Scholar
  23. 23.
    Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451:147–152PubMedCrossRefGoogle Scholar
  24. 24.
    Duan R, Pak C, Jin P (2007) Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet 16:1124–1131PubMedCrossRefGoogle Scholar
  25. 25.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274PubMedCrossRefGoogle Scholar
  26. 26.
    Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966PubMedCrossRefGoogle Scholar
  27. 27.
    Yang R, Schlehe B, Hemminki K, Sutter C, Bugert P, Wappenschmidt B, Volkmann J, Varon R, Weber BH, Niederacher D et al (2010) A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk. Breast Cancer Res Treat 121:693–702PubMedCrossRefGoogle Scholar
  28. 28.
    Tchatchou S, Jung A, Hemminki K, Sutter C, Wappenschmidt B, Bugert P, Weber BH, Niederacher D, Arnold N, Varon-Mateeva R et al (2009) A variant affecting a putative miRNA target site in estrogen receptor (ESR) 1 is associated with breast cancer risk in premenopausal women. Carcinogenesis 30:59–64PubMedCrossRefGoogle Scholar
  29. 29.
    Wu M, Jolicoeur N, Li Z, Zhang L, Fortin Y, L’Abbe D, Yu Z, Shen SH (2008) Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis 29:1710–1716PubMedCrossRefGoogle Scholar
  30. 30.
    Meindl A (2002) Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Int J Cancer 97:472–480PubMedCrossRefGoogle Scholar
  31. 31.
    Arndt V, Sturmer T, Stegmaier C, Ziegler H, Becker A, Brenner H (2003) Provider delay among patients with breast cancer in Germany: a population-based study. J Clin Oncol 21:1440–1446PubMedCrossRefGoogle Scholar
  32. 32.
    Widschwendter M, Apostolidou S, Raum E, Rothenbacher D, Fiegl H, Menon U, Stegmaier C, Jacobs IJ, Brenner H (2008) Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS One 3:e2656PubMedCrossRefGoogle Scholar
  33. 33.
    Gao L, Weck MN, Michel A, Pawlita M, Brenner H (2009) Association between chronic atrophic gastritis and serum antibodies to 15 Helicobacter pylori proteins measured by multiplex serology. Cancer Res 69:2973–2980PubMedCrossRefGoogle Scholar
  34. 34.
    Dupont WD, Plummer WD Jr (1998) Power and sample size calculations for studies involving linear regression. Control Clin Trials 19:589–601PubMedCrossRefGoogle Scholar
  35. 35.
    Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284PubMedCrossRefGoogle Scholar
  36. 36.
    Liu B, Peng XC, Zheng XL, Wang J, Qin YW (2009) MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 66:169–175PubMedCrossRefGoogle Scholar
  37. 37.
    Markham NR, Zuker M (2005) DINAMelt web server for nucleic acid melting prediction. Nucleic Acids Res 33:W577–W581PubMedCrossRefGoogle Scholar
  38. 38.
    Christensen BC, Avissar-Whiting M, Ouellet LG, Butler RA, Nelson HH, McClean MD, Marsit CJ, Kelsey KT (2010) Mature microRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer. Clin Cancer Res 16:3713–3720PubMedCrossRefGoogle Scholar
  39. 39.
    Lee HC, Kim JG, Chae YS, Sohn SK, Kang BW, Moon JH, Jeon SW, Lee MH, Lim KH, Park JY et al (2010) Prognostic impact of microRNA-related gene polymorphisms on survival of patients with colorectal cancer. J Cancer Res Clin Oncol 136:1073–1078PubMedCrossRefGoogle Scholar
  40. 40.
    Qi P, Dou TH, Geng L, Zhou FG, Gu X, Wang H, Gao CF (2010) Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection. Hum Immunol 71:621–626PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Rongxi Yang
    • 1
    • 2
  • Michelle Dick
    • 1
    • 2
  • Frederik Marme
    • 1
  • Andreas Schneeweiss
    • 1
  • Anne Langheinz
    • 1
    • 2
  • Kari Hemminki
    • 3
    • 4
  • Christian Sutter
    • 5
  • Peter Bugert
    • 6
  • Barbara Wappenschmidt
    • 7
  • Raymonda Varon
    • 8
  • Sarah Schott
    • 1
  • Bernhard H. F. Weber
    • 9
  • Dieter Niederacher
    • 10
  • Norbert Arnold
    • 11
  • Alfons Meindl
    • 12
  • Claus R. Bartram
    • 5
  • Rita K. Schmutzler
    • 7
  • Heiko Müller
    • 13
  • Volker Arndt
    • 13
  • Hermann Brenner
    • 13
  • Christof Sohn
    • 1
  • Barbara Burwinkel
    • 1
    • 2
  1. 1.Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of HeidelbergHeidelbergGermany
  2. 2.Helmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  4. 4.Department of Biosciences at NovumKarolinska InstituteHuddingeSweden
  5. 5.Institute of Human GeneticsUniversity of HeidelbergHeidelbergGermany
  6. 6.Medical Faculty of Mannheim, Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-HessenUniversity of HeidelbergMannheimGermany
  7. 7.Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of CologneCologneGermany
  8. 8.Institute of Human Genetics, CharitéHumboldt UniversityBerlinGermany
  9. 9.Institute of Human GeneticsUniversity of RegensburgRegensburgGermany
  10. 10.Division of Molecular Genetics, Department of Gynaecology and ObstetricsClinical Center University of DüsseldorfDüsseldorfGermany
  11. 11.Division of Oncology, Department of Gynaecology and ObstetricsUniversity Hospital Schleswig-HolsteinKielGermany
  12. 12.Department of Gynaecology and ObstetricsKlinikum rechts der Isar, Technical University of MunichMunichGermany
  13. 13.Division of Clinical Epidemiology and Aging ResearchGerman Cancer Research CenterHeidelbergGermany

Personalised recommendations