BACKGROUND/AIM:Circadian rhythm is an internal clock that regulates the cycles of many biological functions. Epidemiological studies have linked aberrant circadian rhythm to an increased susceptibility to cancer and poor patient prognosis. However, there remains a gap in our understanding of genetic variants related to the circadian pathway in renal cell carcinoma (RCC) progression.PATIENTS AND METHODS:We examined the associations of 150 single nucleotide polymorphisms (SNPs) in 12 core circadian pathway genes with RCC risk and survival in 630 patients with RCC and controls.RESULTS:After adjusting for multiple comparisons and performing multivariate analyses, we found that the HLF rs6504958 polymorphism was significantly associated with RCC risk (q0.05), whereas, no SNP association was significant for survival. Furthermore, the rs6504958 G allele was associated with reduced expression of HLF; consequently, a lower HLF expression was correlated with more advanced RCC. Moreover, a meta-analysis of six kidney cancer gene expression datasets demonstrated that an elevated HLF expression was associated with a favorable prognosis in patients with RCC (hazard ratio=0.70, 95% confidence interval=0.65-0.76, p0.001).CONCLUSION:These findings implicate the potential protective role of HLF in the progression of RCC.Copyright? 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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机译：背景/目的：昼夜节律是一个内部时钟，调节许多生物功能的周期。流行病学研究将异常的昼夜节律与癌症和患者预后的易感性增加。然而，在我们对肾细胞癌（RCC）进展中昼夜途径相关的遗传变异仍然存在差距.Patient和方法：我们检查了12个核心昼核途径基因中的150个单核苷酸多态性（SNP）与RCC的关联630例RCC和对照患者的风险和生存。结果：调整多种比较并进行多元分析后，我们发现HLF RS6504958多态性与RCC风险显着相关（Q <0.05），而且没有SNP关联对于生存。此外，RS6504958g等位基因与HLF的表达减少有关;因此，较低的HLF表达与更高级的RCC相关。此外，六种肾癌基因表达数据集的荟萃分析表明，升高的HLF表达与RCC患者的良好预后有关（危害比率= 0.70,95％置信区间= 0.65-0.76，P <0.001）。结论：这些发现隐患了HLF在RCC.Copyright进展中的潜在保护作用？ 2020年，国际抗癌研究所（George J. Delinasios博士），保留所有权利。
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