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
1Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813 Taiwan.
2Department of Urology, School of Medicine, National Yang-Ming University, Taipei, 112 Taiwan.
Cancer Cell Int. 2019 Apr 5;19:87. doi: 10.1186/s12935-019-0811-4. eCollection 2019.
To determine the association between circadian pathway genetic variants and the risk of prostate cancer progression.
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.
A single nucleotide polymorphism of the neuronal PAS domain protein 2 () gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized ( = 0.001) and advanced ( = 0.039) prostate cancer cases. In silico analysis revealed decreased expression levels of in carriers of the T allele of rs6542993 compared with those carrying the A allele. Consistently, downregulation of expression was associated with more aggressive prostate cancer and poor progression-free survival (log-rank = 0.002).
The rs6542993 polymorphism may be a promising biomarker, and may shed light on the pathways that govern prostate cancer progression.
确定昼夜节律途径基因变异与前列腺癌进展风险之间的关联。
在458例局限性前列腺癌患者队列中，作为发现阶段，我们系统评估了9个昼夜节律途径基因中的79个种系变异。然后，我们在另一组324例患有更晚期疾病的男性中重复了这些重要发现。通过对数秩检验和Cox回归评估每个变异与前列腺癌进展的关联。
发现神经元PAS结构域蛋白2（）基因的一个单核苷酸多态性（rs6542993 A>T）与局限性前列腺癌（=0.001）和晚期前列腺癌（=0.039）病例中显著更高的疾病进展风险相关。生物信息学分析显示，与携带A等位基因的个体相比，rs6542993 T等位基因携带者中表达水平降低。同样，表达下调与侵袭性更强的前列腺癌和无进展生存期较差相关（对数秩=0.002）。
rs6542993多态性可能是一种有前景的生物标志物，并可能揭示控制前列腺癌进展的途径。
