Breast Cancer Research and Treatment

, Volume 107, Issue 3, pp 421–425 | Cite as

Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk

  • Yong Zhu
  • Richard G. Stevens
  • Derek Leaderer
  • Aaron Hoffman
  • Theodore Holford
  • Yawei Zhang
  • Heather N. Brown
  • Tongzhang Zheng


Three known non-synonymous polymorphisms (Ala394Thr, Ser471Leu and Pro690Ala) in the largest circadian gene, Neuronal PAS domain protein 2 (NPAS2), were genotyped in a breast cancer case-control study conducted in Connecticut, USA (431 cases and 476 controls). We found that women with the heterozygous Ala394Thr genotype were significantly associated with breast cancer risk compared to those with the common homozygous Ala394Ala (OR = 0.61, 0.46–0.81, P = 0.001). This is the first evidence demonstrating a role of the circadian gene NPAS2 in human breast cancer, suggesting that genetic variations in circadian genes might be a novel panel of biomarkers for breast cancer risk.


Circadian gene NPAS2 Breast cancer 



This study was supported by funds from Yale University. The work was also supported by the NIH grants CA62986, CA110937, CA108369, ES11659 and CA122676.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Yong Zhu
    • 1
  • Richard G. Stevens
    • 2
  • Derek Leaderer
    • 1
  • Aaron Hoffman
    • 1
  • Theodore Holford
    • 1
  • Yawei Zhang
    • 1
  • Heather N. Brown
    • 1
  • Tongzhang Zheng
    • 1
  1. 1.Department of Epidemiology and Public HealthYale University School of MedicineNew HavenUSA
  2. 2.University of Connecticut Health CenterFarmingtonUSA

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