A functional polymorphism in PER3 gene is associated with prognosis in hepatocellular carcinoma

• Published in: Liver international 2012-10, Vol.32 (9), p.1451-1459
• Main Authors: Zhao, Binyu, Lu, Jianguo, Yin, Jikai, Liu, Hanqiang, Guo, Xu, Yang, Yefa, Ge, Naijian, Zhu, Yong, Zhang, Hongxin, Xing, Jinliang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - therapy; Cell cycle; Cell proliferation; Chemoembolization, Therapeutic; Chemotherapy; China - epidemiology; circadian gene; Circadian Rhythm - genetics; Circadian rhythms; Data processing; DNA damage; Feedback; Female; Gene polymorphism; Gene regulation; Genetic Predisposition to Disease; Genotype; Genotyping; Hepatocellular carcinoma; Humans; Kaplan-Meier Estimate; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - therapy; Male; Middle Aged; Period 1 protein; Period 2 protein; Period 3 protein; Period Circadian Proteins - genetics; Polymorphism, Single Nucleotide; Prognosis; Single-nucleotide polymorphism; Survival; Survival Rate; Transcription; Young Adult
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2012.02849.x

Background 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. Aims We hypothesized that the polymorphisms in circadian genes may be associated with prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). Methods 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. Results 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). Conclusions 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.