These authors contributed equally to this work.
Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization-treated hepatocellular carcinoma patients
Article first published online: 18 JUN 2014
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 7, pages 825–832, July 2014
How to Cite
Cancer Sci (2014) 825–832
National Natural Science Foundation (81201583 and 81171966). International S&T Cooperation Program (s2011gr0239). National Key Scientific and Technological Project (2011ZX09307-001-04) from the Ministry of Science and Technology of China.
- Issue published online: 14 JUL 2014
- Article first published online: 18 JUN 2014
- Accepted manuscript online: 23 APR 2014 05:04AM EST
- Manuscript Accepted: 18 APR 2014
- Manuscript Revised: 31 MAR 2014
- Manuscript Received: 29 DEC 2013
- National Natural Science Foundation. Grant Numbers: 81201583, 81171966
- International S&T Cooperation Program of China. Grant Number: s2011gr0239
- Ministry of Science and Technology of China. Grant Number: 2011ZX09307-001-04
- Hepatocellular carcinoma;
- NPAS2 ;
- single nucleotide polymorphism;
- transcatheter arterial chemoembolization
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.