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

Breast Cancer Res Treat. 2008 Feb;107(3):421-5. doi: 10.1007/s10549-007-9565-0. Epub 2007 Apr 24.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Breast Neoplasms / etiology
  • Breast Neoplasms / genetics*
  • Circadian Rhythm / genetics*
  • Female
  • Genotype
  • Humans
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Genetic*
  • Risk Factors


  • Basic Helix-Loop-Helix Transcription Factors
  • NPAS2 protein, human
  • Nerve Tissue Proteins