Breast Cancer Research and Treatment

, Volume 121, Issue 3, pp 693–702

A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk

  • Rongxi Yang
  • Bettina Schlehe
  • Kari Hemminki
  • Christian Sutter
  • Peter Bugert
  • Barbara Wappenschmidt
  • Juliane Volkmann
  • Raymonda Varon
  • Bernhard H. F. Weber
  • Dieter Niederacher
  • Norbert Arnold
  • Alfons Meindl
  • Claus R. Bartram
  • Rita K. Schmutzler
  • Barbara Burwinkel
Epidemiology

DOI: 10.1007/s10549-009-0633-5

Cite this article as:
Yang, R., Schlehe, B., Hemminki, K. et al. Breast Cancer Res Treat (2010) 121: 693. doi:10.1007/s10549-009-0633-5

Abstract

MicroRNAs (miRNAs) regulate pathways involved in cell differentiation, proliferation, development, and apoptosis by degradation of target mRNAs and/or repression of their translation. Although the single nucleotide polymorphisms (SNPs) in miRNAs target sites have been studied, the effects of SNPs in miRNAs are largely unknown. In our study, we first systematically sequenced miRNA genes reported to be involved in breast cancer to identify/verify SNPs. We analyzed four SNPs, one located in the pre-miRNA and the other three located in miRNA flanking regions, for a putative association with breast cancer risk. The SNP rs895819, located in the terminal loop of pre-miRNA-27a, showed a protective effect. In a large familial breast cancer study cohort, the rare [G] allele of rs895819 was found to be less frequent in the cases than in the controls, indicating a reduced familial breast cancer risk ([G] vs. [A]: OR = 0.88, 95% CI 0.78–0.99, P = 0.0287). Furthermore, age stratification revealed that the protective effect was mainly observed in the age group < 50 years of age ([G] vs. [A]: OR = 0.83, 95% CI 0.70–0.98, P = 0.0314), whereas no significant effect was observed in the age group ≥ 50 years of age, indicating a possible hormone-related effect. It has been shown that artificial mutations in the terminal loop of miR-27a can block the maturation process of the miRNA. We hypothesize that the G-variant of rs895819 might impair the maturation of the oncogenic miR-27a and thus, is associated with familial breast cancer risk.

Keywords

Breast cancer riskMicroRNASNPCase–control study

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Rongxi Yang
    • 1
    • 2
  • Bettina Schlehe
    • 2
  • Kari Hemminki
    • 3
    • 4
  • Christian Sutter
    • 5
  • Peter Bugert
    • 6
  • Barbara Wappenschmidt
    • 7
  • Juliane Volkmann
    • 8
  • Raymonda Varon
    • 9
  • Bernhard H. F. Weber
    • 10
  • Dieter Niederacher
    • 11
  • Norbert Arnold
    • 12
  • Alfons Meindl
    • 8
  • Claus R. Bartram
    • 5
  • Rita K. Schmutzler
    • 7
  • Barbara Burwinkel
    • 1
    • 2
  1. 1.Helmholtz-University Group Molecular EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of HeidelbergHeidelbergGermany
  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.Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-HessenUniversity of Heidelberg, Medical Faculty of MannheimMannheimGermany
  7. 7.Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of CologneCologneGermany
  8. 8.Department of Gynaecology and ObstetricsKlinikum rechts der Isar, Technical University of MunichMunichGermany
  9. 9.Institute of Human Genetics, CharitéHumboldt UniversityBerlinGermany
  10. 10.Institute of Human GeneticsUniversity of RegensburgRegensburgGermany
  11. 11.Division of Molecular Genetics, Department of Gynaecology and ObstetricsClinical Center University of DüsseldorfDüsseldorfGermany
  12. 12.Division of Oncology, Department of Gynaecology and ObstetricsUniversity Hospital Schleswig-HolsteinKielGermany