The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer.
Mounting evidence suggests that neuronal PAS domain protein 2 (NPAS2) and other circadian genes are involved in tumorigenesis and tumor growth, possibly through their control of cancer-related biologic pathways. A missense polymorphism in NPAS2 (Ala394Thr) has been shown to be associated with risk of human tumors including breast cancer. The current study further examined the prognostic significance of NPAS2 in breast cancer by genotyping the Ala394Thr polymorphism and measuring NPAS2 expression. DNA extracted from 348 breast cancer tissue samples was analyzed for NPAS2 genotype using the TaqMan allelic discrimination assay. Of these, 287 also had total RNA available for use in real-time PCR assays to determine NPAS2 expression. NPAS2 genotypes and expression levels were analyzed for associations with prognostic outcomes, as well as correlations with clinical characteristics. A high level of NPAS2 expression was strongly associated with improved disease free survival (AHR = 0.43, 95% CI: 0.21-0.86, P trend = 0.022) and overall survival (AHR = 0.42, 95% CI: 0.19-0.96, P trend = 0.036). In addition, there was a borderline, but nonsignificant association between the NPAS2 genotype corresponding to Thr394Thr and disease free survival (AHR = 1.82, 95% CI: 0.96-3.46). The Ala/Ala, Ala/Thr, and Thr/Thr genotypes were also differentially distributed by tumor severity, as measured by TNM classification (chi (2) (6df, N = 344) = 14.96, P = 0.020). These findings provide the first evidence suggesting prognostic significance of the circadian gene NPAS2 in breast cancer.
Yi
Chunhui
C
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, 06520, USA.
Mu
Lina
L
de la Longrais
Irene A Rigault
IA
Sochirca
Olga
O
Arisio
Riccardo
R
Yu
Herbert
H
Hoffman
Aaron E
AE
Zhu
Yong
Y
Katsaro
Dionyssios
D
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D002940:Circadian Rhythm / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C104264:NPAS2 protein, human