Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression

Chia Cheng Yu, Lih Chyang Chen, Chih Yung Chiou, Yu Jia Chang, Victor C. Lin, Chao Yuan Huang, I. Ling Lin, Ta Yuan Chang, Te Ling Lu, Cheng Hsueh Lee, Shu Pin Huang, Bo Ying Bao

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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.

Original languageEnglish
Article number87
JournalCancer Cell International
Volume19
Issue number1
DOIs
Publication statusPublished - Apr 5 2019

Keywords

  • Circadian rhythm
  • NPAS2
  • Progression
  • Prostate cancer
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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  • Cite this

    Yu, C. C., Chen, L. C., Chiou, C. Y., Chang, Y. J., Lin, V. C., Huang, C. Y., Lin, I. L., Chang, T. Y., Lu, T. L., Lee, C. H., Huang, S. P., & Bao, B. Y. (2019). Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression. Cancer Cell International, 19(1), [87]. https://doi.org/10.1186/s12935-019-0811-4