Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization‐treated hepatocellular carcinoma patients

Cancer Science

Peng Yuan⁵  Shen Wang⁵  Feng Zhou³  Shaogui Wan¹  Yefa Yang⁴  Xiaojun Huang¹  Zhaohui Zhang³  Yong Zhu²  Hongxin Zhang⁵ 

[1] State Key Laboratory of Cancer Biology, Experimental Teaching Center of Basic Medicine, The Fourth Military Medical University, Xi'an, China;Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA;Department of General Surgery, Affiliated Huaihai Hospital of Xuzhou Medical College, Xuzhou, China;Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China;Department of Pain Management, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China

关键词: Hepatocellular carcinoma;    NPAS2;    prognosis;    single nucleotide polymorphism;    transcatheter arterial chemoembolization;   

DOI  :  10.1111/cas.12428

来源: Wiley

【 摘 要 】

Abstract

The functional abnormality of circadian regulation genes is involved in the development and progression of hepatocellular carcinoma (HCC). However, the association between functional single nucleotide polymorphisms (SNPs) in circadian gene NPAS2 and the overall survival of HCC patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Six functional SNPs in the NPAS2 gene were genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese patients with HCC treated with TACE. Multivariate Cox proportional hazards model and Kaplan–Meier curves were used for the prognosis analysis. We found that two SNPs, rs1053096 and rs2305160, in the NPAS2 gene showed significant associations with overall death risk in HCC patients in the recessive model (hazard ratio [HR] = 1.48; 95% confidence interval [CI], 1.13–1.94; P = 0.004) and in the dominant model (HR = 1.63; 95% CI, 1.29–2.07; P < 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of increasing death risk with increasing number of unfavorable genotypes (P for trend < 0.001). Compared with the patients without any unfavorable genotypes, the HRs for patients with one and two unfavorable genotypes were 1.41 (95% CI, 1.10–1.82; P = 0.007) and 2.09 (95% CI, 1.46–2.97, P < 0.001), respectively. The haplotype and diplotype analyses further characterized the association between NPAS2 genotype and survival of HCC patients. Our results for the first time suggest that NPAS2 gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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