The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer

Yi, Chunhui; Mu, Lina; Longrais, Irene A. Rigault de la; Sochirca, Olga; Arisio, Riccardo; Yu, Herbert; Hoffman, Aaron E.; Zhu, Yong; Katsaro, Dionyssios

doi:10.1007/s10549-009-0484-0

Cited by 66 publications

(51 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a high level of NPAS2 expression was strongly associated with improved diseasefree survival (HR = 0.43, 95% CI: 0.21-0.86, P trend = 0.022) and overall survival (HR = 0.42, 95% CI: 0.19-0.96, P trend = 0.036) [15]. Thus, it's reasonable to hypothesis that the genetic and expression variations of NPAS2 will be in relation to clinical characteristics of breast cancer and breast cancer survival.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, the same group also reported that rs2305160 may borderline significantly related to breast cancer survival, where as NPAS2 expression is a significant biomarker for breast cancer survival [15]. As NPAS2 is a trans-activator to control the expression of downstream tumor-related genes, we searched potentially functional SNPs in the promoter region, 5 0 -untranslated region (UTR) and 3 0 UTR, which may influence gene expression, and found a putative functional SNP (rs3739008) located at 3 0 UTR of NPAS2.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk

Wang

Yang

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

Disruption of the circadian rhythm has been reported to increase the risk of breast cancer. A single nucleotide polymorphism (SNP) rs2305160 in Neuronal PAS domain protein 2 (NPAS2), the largest circadian gene, was identified as a breast cancer susceptibility locus. In the current study, we found a novel functional SNP (rs3739008) located at 3'UTR of NPAS2 and the C to T changing of the SNP may disrupt the binding of microRNA- (miR-) 17-5p and miR-519e to the 3'UTR of NPAS2. We then typed this SNP in case-control studies of both Chinese and Germany populations to test its putative associations with breast cancer risk. However, we failed to find any significant associations by different genetic models (dominant genetic model, adjusted OR = 1.13, 95% CI = 0.95-1.35 for the Chinese population and adjusted OR = 0.99, 95% CI = 0.85-1.16 for the Germany population). Although we did not find significant associations at population levels from both Chinese and Germany case-control studies, due to the functional relevance of rs3739008 on NASP2 expression, it will be promising to investigate the influence of this variant on clinical characteristics of breast cancer and breast cancer survival.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 92%

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk

Wang

Yang

et al. 2010

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…Population based studies have identified associations with variants in circadian pathways genes and risk of breast cancer [2–4], prostate cancer [5, 6] and non-Hodgkin’s lymphoma [7, 8]. Variants in these genes have also been associated with survival in hepatocellular carcinoma [9], breast [10], prostate [11] and colon [12] cancer.…”

Section: Introductionmentioning

confidence: 99%

Circadian pathway genes in relation to glioma risk and outcome

Madden

Anic

Thompson

et al. 2013

Cancer Causes Control

View full text Add to dashboard Cite

Purpose There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case-control study. Methods Subjects were genotyped for 17 candidate single nucleotide polymorphisms (SNPs) in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant and recessive). Proportional hazards regression was used to estimate hazard ratios (HR) for glioma-related death among 441 patients with high grade tumors. Survival associations were validated using a TCGA (The Cancer Genome Atlas) dataset. Results A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR: 0.80; 95% CI: 0.66–0.97; ptrend=0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR: 2.41; 95% CI: 1.31–4.42; p=0.005), though not other glioma subtypes (p for heterogeneity=0.0033). The association remained significant after FDR adjustment (p=0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in GBM versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, PER3) and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients. Conclusion This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.

show abstract

“…This was shown for colorectal cancer, 40,41 chronic lymphocytic leukemia, 42 epithelial ovarian cancer, 43 and breast cancer. 44 In various epidemiological studies, it was shown that single nucleotide polymorphisms in clock genes are associated with higher cancer risk for prostate cancer (CRY2 rs1401417: G.C, 1.7-fold higher risk), 45 breast cancer (NPAS2 Ala394Thr), 46 non-Hodgkin's lymphoma (CRY2 rs11038689, rs7123390, rs1401417), 47 and colorectal carcinoma (CLOCK1 311T.C, CC 2.78-fold and TC 1.78-fold higher risk). 48 Gene expression of all three PERs is deregulated in breast cancer cells, and PER1 expression is downregulated in most patients.…”

Section: Circadian Rhythms and Cancermentioning

confidence: 99%

Circadian rhythms and new options for novel anticancer therapies

Zmrzljak¹

2015

CPT

View full text Add to dashboard Cite

The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.

show abstract

The circadian gene NPAS2 is a novel prognostic biomarker for breast cancer

Cited by 66 publications

References 27 publications

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk

A variant affecting miRNAs binding in the circadian gene Neuronal PAS domain protein 2 (NPAS2) is not associated with breast cancer risk

Circadian pathway genes in relation to glioma risk and outcome

Circadian rhythms and new options for novel anticancer therapies

Contact Info

Product

Resources

About