Department of Pain Medicine, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Liver Int. 2012 Oct;32(9):1451-9. doi: 10.1111/j.1478-3231.2012.02849.x. Epub 2012 Jul 19.
Previous studies have revealed that circadian genes play important roles in cell proliferation, apoptosis, cell cycle control, DNA damage response and treatment response of chemotherapy agents in cancers.
We hypothesized that the polymorphisms in circadian genes may be associated with prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE).
Twelve functional single nucleotide polymorphisms (SNPs) in circadian negative feedback regulation genes (including CRY1, CRY2, PER1, PER2 and PER3) were genotyped using Sequenom iPLEX genotyping method in 337 HCC patients treated with TACE and analysed for associations with overall survival.
Our data showed that one SNP rs2640908 in PER3 gene was significantly associated with overall survival of HCC patients (P = 0.027). Patients carrying at least one variant allele of rs2640908 (WV + VV) had a significantly decreased risk of death (hazard ratio, 0.71; 95% confidence interval, 0.53-0.90), when compared with those carrying homozygous wild-type alleles (WW). Kaplan-Meier analyses showed a significantly longer median survival time in patients with WV + VV genotypes of SNP rs2640908 than those with WW genotype (11.6 months vs. 8.1 months; log rank P = 0.030). In addition, we also observed a significant difference on the genotype distribution of SNP rs2640908 in patients with and without portal vein thrombus (P = 0.041).
Our study provides the first evidence that a single functional polymorphism of PER3 gene is significantly associated with overall survival in HCC patients treated with TACE.
先前的研究表明，生物钟基因在癌症中的细胞增殖、凋亡、细胞周期控制、DNA 损伤反应和化疗药物治疗反应中发挥着重要作用。
我们假设生物钟基因的多态性可能与接受经导管肝动脉化疗栓塞术（TACE）治疗的肝细胞癌（HCC）患者的预后相关。
采用Sequenom iPLEX 基因分型方法对 337 例接受 TACE 治疗的 HCC 患者的 12 个生物钟负反馈调节基因（包括 CRY1、CRY2、PER1、PER2 和 PER3）中的 12 个功能性单核苷酸多态性（SNP）进行基因分型，并分析其与总生存期的关系。
我们的数据显示，PER3 基因中的一个 SNP rs2640908 与 HCC 患者的总生存期显著相关（P=0.027）。与携带纯合野生型等位基因（WW）的患者相比，携带至少一个 rs2640908 变异等位基因（WV+VV）的患者死亡风险显著降低（危险比，0.71；95%置信区间，0.53-0.90）。Kaplan-Meier 分析显示，rs2640908 的 WV+VV 基因型患者的中位生存时间明显长于 WW 基因型患者（11.6 个月比 8.1 个月；对数秩检验 P=0.030）。此外，我们还观察到 SNP rs2640908 的基因型分布在有和无门静脉血栓形成的患者之间存在显著差异（P=0.041）。
本研究首次提供证据表明，PER3 基因的单个功能性多态性与接受 TACE 治疗的 HCC 患者的总生存期显著相关。
