Zhu Yong, Stevens Richard G, Leaderer Derek, Hoffman Aaron, Holford Theodore, Zhang Yawei, Brown Heather N, Zheng Tongzhang
Department of Epidemiology and Public Health, Yale University School of Medicine, LEPH Room 702, New Haven, CT 06520, USA.
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.
在美国康涅狄格州进行的一项乳腺癌病例对照研究中，对最大的昼夜节律基因——神经元PAS结构域蛋白2（NPAS2）中的三个已知非同义多态性（Ala394Thr、Ser471Leu和Pro690Ala）进行了基因分型（431例病例和476例对照）。我们发现，与常见的纯合子Ala394Ala相比，携带杂合子Ala394Thr基因型的女性与乳腺癌风险显著相关（OR = 0.61，0.46 - 0.81，P = 0.001）。这是证明昼夜节律基因NPAS2在人类乳腺癌中起作用的首个证据，表明昼夜节律基因的遗传变异可能是一组新的乳腺癌风险生物标志物。
