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Breast Cancer Research and Treatment

, Volume 127, Issue 3, pp 769–775 | Cite as

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk

  • Furu Wang
  • Zhibin Hu
  • Rongxi Yang
  • Jinhai Tang
  • Yao Liu
  • Kari Hemminki
  • Christian Sutter
  • Barbara Wappenschmidt
  • Dieter Niederacher
  • Norbert Arnold
  • Alfons Meindl
  • Claus R. Bartram
  • Rita K. Schmutzler
  • Barbara Burwinkel
  • Hongbing ShenEmail author
Epidemiology

Abstract

Disruption of the circadian rhythm has been reported to increase the risk of breast cancer. A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus. In the current study, we found a novel functional SNP (rs3739008) located at 3′UTR of NPAS2 and the C to T changing of the SNP may disrupt the binding of microRNA- (miR-) 17-5p and miR-519e to the 3′UTR of NPAS2. We then typed this SNP in case–control studies of both Chinese and Germany populations to test its putative associations with breast cancer risk. However, we failed to find any significant associations by different genetic models (dominant genetic model, adjusted OR = 1.13, 95% CI = 0.95–1.35 for the Chinese population and adjusted OR = 0.99, 95% CI = 0.85–1.16 for the Germany population). Although we did not find significant associations at population levels from both Chinese and Germany case–control studies, due to the functional relevance of rs3739008 on NASP2 expression, it will be promising to investigate the influence of this variant on clinical characteristics of breast cancer and breast cancer survival.

Keywords

NPAS2 miRNAs SNPs Breast cancer Molecular epidemiology 

Abbreviations

NPAS2

Neuronal PAS domain protein 2

SNPs

single nucleotide polymorphisms

UTR

untranslated region

miRNAs

microRNAs

OR

odds-ratio

CI

confidence interval

Notes

Acknowlegments

The study was supported in part by Program for Changjiang Scholars and Innovative Research Team in University (IRT0631); Jiangsu Society Development Foundation (BS2006006); Key project of Nature Science Foundation of Jiangsu Colleges (09KJA330001); the Deutsche Krebshilfe (Grant number: 107054); the Helmholtz Society (VH-NG-213); and the Dietmar-Hopp Foundations.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Furu Wang
    • 1
  • Zhibin Hu
    • 1
    • 2
    • 3
  • Rongxi Yang
    • 2
    • 3
  • Jinhai Tang
    • 4
  • Yao Liu
    • 1
  • Kari Hemminki
    • 5
    • 6
  • Christian Sutter
    • 7
  • Barbara Wappenschmidt
    • 8
  • Dieter Niederacher
    • 9
  • Norbert Arnold
    • 10
  • Alfons Meindl
    • 11
  • Claus R. Bartram
    • 7
  • Rita K. Schmutzler
    • 8
  • Barbara Burwinkel
    • 2
    • 3
  • Hongbing Shen
    • 1
    Email author
  1. 1.Laboratory of Reproductive Medicine, Cancer CenterNanjing Medical UniversityNanjingChina
  2. 2.Helmholtz-University Group Molecular EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of HeidelbergHeidelbergGermany
  4. 4.Department of General SurgeryJiangsu Cancer HospitalNanjingChina
  5. 5.Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  6. 6.Department of Biosciences at NovumKarolinska InstituteHuddingeSweden
  7. 7.Institute of Human GeneticsUniversity of HeidelbergHeidelbergGermany
  8. 8.Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of CologneCologneGermany
  9. 9.Division of Molecular Genetics, Department of Gynaecology and ObstetricsClinical Center University of DüsseldorfDüsseldorfGermany
  10. 10.Division of Oncology, Department of Gynaecology and ObstetricsUniversity Hospital Schleswig-HolsteinKielGermany
  11. 11.Department of Gynaecology and Obstetrics, Klinikum rechts der IsarTechnical University of MunichMunichGermany

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