Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression
Journal
Cancer Cell International
Journal Volume
19
Journal Issue
1
Pages
87
Date Issued
2019
Author(s)
Yu C.-C.
Chen L.-C.
Chiou C.-Y.
Chang Y.-J.
Lin V.C.
Lin I.-L.
Chang T.-Y.
Lu T.-L.
Lee C.-H.
Huang S.-P.
Bao B.-Y.
Abstract
Background: To determine the association between circadian pathway genetic variants and the risk of prostate cancer progression. Methods: We systematically evaluated 79 germline variants in nine circadian pathway genes in a cohort of 458 patients with localized prostate cancer as the discovery phase. We then replicated the significant findings in another cohort of 324 men with more advanced disease. The association of each variant with prostate cancer progression was evaluated by a log-rank test and Cox regression. Results: A single nucleotide polymorphism of the neuronal PAS domain protein 2 (NPAS2) gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized (P = 0.001) and advanced (P = 0.039) prostate cancer cases. In silico analysis revealed decreased expression levels of NPAS2 in carriers of the T allele of rs6542993 compared with those carrying the A allele. Consistently, downregulation of NPAS2 expression was associated with more aggressive prostate cancer and poor progression-free survival (log-rank P = 0.002). Conclusions: The NPAS2 rs6542993 polymorphism may be a promising biomarker, and may shed light on the pathways that govern prostate cancer progression. ? 2019 The Author(s).
Subjects
Circadian rhythm; NPAS2; Progression; Prostate cancer; Single nucleotide polymorphism
SDGs
Other Subjects
adult; advanced cancer; aged; allele; Article; cancer growth; cancer risk; circadian rhythm; cohort analysis; gene; gene expression regulation; genetic association; genetic variability; genotype; human; major clinical study; male; NPAS2 gene; progression free survival; prostate cancer; risk factor; single nucleotide polymorphism; survival rate
Publisher
BioMed Central Ltd.
Type
journal article