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

Research output: Contribution to journalArticle

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

Fingerprint

Circadian Rhythm
Prostatic Neoplasms
Alleles
Computer Simulation
Disease-Free Survival
Single Nucleotide Polymorphism
Disease Progression
Down-Regulation
Biomarkers
Protein Domains
Genes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression. / Yu, Chia Cheng; Chen, Lih Chyang; Chiou, Chih Yung; Chang, Yu Jia; Lin, Victor C.; Huang, Chao Yuan; Lin, I. Ling; Chang, Ta Yuan; Lu, Te Ling; Lee, Cheng Hsueh; Huang, Shu Pin; Bao, Bo Ying.

In: Cancer Cell International, Vol. 19, No. 1, 87, 05.04.2019.

Research output: Contribution to journalArticle

Yu, CC, Chen, LC, Chiou, CY, Chang, YJ, Lin, VC, Huang, CY, Lin, IL, Chang, TY, Lu, TL, Lee, CH, Huang, SP & Bao, BY 2019, 'Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression', Cancer Cell International, vol. 19, no. 1, 87. https://doi.org/10.1186/s12935-019-0811-4
Yu, Chia Cheng ; Chen, Lih Chyang ; Chiou, Chih Yung ; Chang, Yu Jia ; Lin, Victor C. ; Huang, Chao Yuan ; Lin, I. Ling ; Chang, Ta Yuan ; Lu, Te Ling ; Lee, Cheng Hsueh ; Huang, Shu Pin ; Bao, Bo Ying. / Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression. In: Cancer Cell International. 2019 ; Vol. 19, No. 1.
@article{64a0b06d35934bc8adec5fafc8d93bd7,
title = "Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression",
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.",
keywords = "Circadian rhythm, NPAS2, Progression, Prostate cancer, Single nucleotide polymorphism",
author = "Yu, {Chia Cheng} and Chen, {Lih Chyang} and Chiou, {Chih Yung} and Chang, {Yu Jia} and Lin, {Victor C.} and Huang, {Chao Yuan} and Lin, {I. Ling} and Chang, {Ta Yuan} and Lu, {Te Ling} and Lee, {Cheng Hsueh} and Huang, {Shu Pin} and Bao, {Bo Ying}",
year = "2019",
month = "4",
day = "5",
doi = "10.1186/s12935-019-0811-4",
language = "English",
volume = "19",
journal = "Cancer Cell International",
issn = "1475-2867",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Genetic variants in the circadian rhythm pathway as indicators of prostate cancer progression

AU - Yu, Chia Cheng

AU - Chen, Lih Chyang

AU - Chiou, Chih Yung

AU - Chang, Yu Jia

AU - Lin, Victor C.

AU - Huang, Chao Yuan

AU - Lin, I. Ling

AU - Chang, Ta Yuan

AU - Lu, Te Ling

AU - Lee, Cheng Hsueh

AU - Huang, Shu Pin

AU - Bao, Bo Ying

PY - 2019/4/5

Y1 - 2019/4/5

N2 - 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.

AB - 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.

KW - Circadian rhythm

KW - NPAS2

KW - Progression

KW - Prostate cancer

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=85063971493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063971493&partnerID=8YFLogxK

U2 - 10.1186/s12935-019-0811-4

DO - 10.1186/s12935-019-0811-4

M3 - Article

AN - SCOPUS:85063971493

VL - 19

JO - Cancer Cell International

JF - Cancer Cell International

SN - 1475-2867

IS - 1

M1 - 87

ER -