title: Functional polymorphisms in the NPAS2 gene are associated with overall survival in transcatheter arterial chemoembolization-treated hepatocellular carcinoma patients.
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.
authors.affiliation: Department of Pain Management, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Shen
authors.initials: S
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Yefa
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Huang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhang
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C104264:NPAS2 protein, human
keywords: Hepatocellular carcinoma; NPAS2; prognosis; single nucleotide polymorphism; transcatheter arterial chemoembolization
references.citation: J Biol Rhythms. 2007 Aug;22(4):291-8
references.pmid: 17660446
references.citation: Nat Neurosci. 2007 May;10(5):543-5
references.pmid: 17417633
references.citation: ScientificWorldJournal. 2013 Mar 27;2013:479805
references.pmid: 23606815
references.citation: Science. 2003 Jul 18;301(5631):379-83
references.pmid: 12843397
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Cancer Sci. 2006 Jul;97(7):589-96
references.pmid: 16827798
references.citation: Annu Rev Pharmacol Toxicol. 2010;50:377-421
references.pmid: 20055686
references.citation: Curr Top Dev Biol. 2007;78:173-216
references.pmid: 17338917
references.citation: Cell. 2001 Dec 28;107(7):855-67
references.pmid: 11779462
references.citation: BMC Cancer. 2010 Sep 03;10:477
references.pmid: 20815902
references.citation: Cancer Lett. 2009 Nov 1;284(2):149-56
references.pmid: 19457610
references.citation: Mol Carcinog. 2008 Dec;47(12):925-33
references.pmid: 18444243
references.citation: Int J Cancer. 2007 Jan 15;120(2):432-5
references.pmid: 17096334
references.citation: Mutat Res. 2009 Nov-Dec;680(1-2):95-105
references.pmid: 19833225
references.citation: Breast Cancer Res Treat. 2008 Feb;107(3):421-5
references.pmid: 17453337
references.citation: Am J Gastroenterol. 2003 May;98(5):1181-5
references.pmid: 12809846
references.citation: Prostate Cancer Prostatic Dis. 2008;11(4):342-8
references.pmid: 17984998
references.citation: Cancer Causes Control. 2006 May;17(4):525-30
references.pmid: 16596306
references.citation: Liver Int. 2012 Oct;32(9):1451-9
references.pmid: 22809120
references.citation: Cancer. 2012 Feb 15;118(4):937-46
references.pmid: 21773969
references.citation: Oncol Rep. 2011 May;25(5):1439-46
references.pmid: 21380491
references.citation: Mol Cancer Res. 2008 Sep;6(9):1461-8
references.pmid: 18819933
references.citation: Lancet. 2012 Mar 31;379(9822):1245-55
references.pmid: 22353262
references.citation: J Natl Cancer Inst. 2013 Jan 2;105(1):59-68
references.pmid: 23150720
references.citation: Breast Cancer Res Treat. 2010 Apr;120(3):663-9
references.pmid: 19649706
references.citation: Chin J Cancer. 2013 Apr;32(4):162-9
references.pmid: 23489585
references.citation: Hepatology. 2005 Nov;42(5):1208-36
references.pmid: 16250051
references.citation: Nat Rev Cancer. 2013 Dec;13(12):827-41
references.pmid: 24263188