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...

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Published in:	Breast cancer research and treatment Vol. 120; no. 3; pp. 663 - 669
Main Authors:	Yi, Chunhui, Mu, Lina, de la Longrais, Irene A. Rigault, Sochirca, Olga, Arisio, Riccardo, Yu, Herbert, Hoffman, Aaron E., Zhu, Yong, Katsaro, Dionyssios
Format:	Journal Article
Language:	English
Published:	Boston Springer US 01-04-2010 Springer Springer Nature B.V
Subjects:	Adenocarcinoma - genetics Adenocarcinoma - mortality Adenocarcinoma - therapy Adult Aged Analysis Basic Helix-Loop-Helix Transcription Factors - analysis Basic Helix-Loop-Helix Transcription Factors - genetics Biological and medical sciences Biomarkers Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Breast cancer Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - therapy Cancer Cancer research Cancer therapies Circadian Rhythm - genetics Disease-Free Survival DNA DNA, Neoplasm - genetics Epidemiology Female Gene expression Gene Expression Regulation, Neoplastic Genes Genes, Tumor Suppressor Genetic aspects Genotype Gynecology. Andrology. Obstetrics Humans Kaplan-Meier Estimate Mammary gland diseases Medical prognosis Medical sciences Medicine Medicine & Public Health Middle Aged Neoplasm Proteins - analysis Neoplasm Proteins - genetics Nerve Tissue Proteins - analysis Nerve Tissue Proteins - genetics Oncology Polymerase Chain Reaction Polymorphism, Single Nucleotide Prognosis Proportional Hazards Models RNA RNA, Messenger - analysis RNA, Neoplasm - analysis Tumors Circadian gene Survival Breast caner Breast disease Prognosis Biological marker Breast cancer Malignant tumor NPAS2 Mammary gland diseases Gene Breast Genetics Mammary gland Cancer
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Summary:	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 ( χ 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-6806 1573-7217
DOI:	10.1007/s10549-009-0484-0