Genetic variants in NPAS2 gene and clinical outcomes of resectable non-small-cell lung cancer.


He Y(1), Wang G(2), Wang Q(3), Zhao Z(4), Gan L(5), Yang S(6), Wang Y(6), Guo S(6), An J(7), Zhang J(8), Zhang Z(8), Zhou F(6)(8).
Author information:
(1)Sun Yat-sen University Medical College, Guangzhou, 510000, China.
(2)Department of General Surgery, The 74th Group Army Hospital, Guangzhou, 510318, China.
(3)Department of Anorectal Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China.
(4)Department of Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, 710032, China.
(5)Department of orthopedics, Air Force Medical Center, Beijing, 100000, China.
(6)Department of Physiology & Pathophysiology, The Fourth Military Medical University, Xi'an, 710032, China.
(7)Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
(8)Department of General Surgery, Huaihai Hospital, Xuzhou Medical University, Xuzhou, Jiangsu, 210000, China.


Background: A series of studies have demonstrated that NPAS2 plays a critical role in the development and progression of several cancers. However, the association between genetic variants in the NPAS2 gene and the clinical outcome of patients with non-small-cell lung cancer (NSCLC) has not been investigated. Methods: Six functional SNPs in NPAS2 were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 484 Chinese NSCLC patients undergoing surgery. Multivariate Cox proportional hazards model were used for the prognosis analysis. Results: We found that SNP rs2305158 exhibited a significant association with overall survival of NSCLC patients in the dominant model (hazard ratio [HR]: 0.68; 95% CI: 0.49-0.95; p = 0.02). Lymph node metastasis was significantly associated with increased death risk (HR: 1.73; 95% CI: 1.24-2.40; p = 0.001) in patients with the homozygous wildtype (WW) genotype of rs2305158. However, no significant association was observed between them in patients carrying a heterozygous variant (WV) or homozygous variant (VV) genotype of rs2305158. Finally, in the joint and interaction analysis, the patients carrying homozygous wildtype (WW) genotype and lymph node metastasis from N1 to N3 conferred a significant increased effect on death (HR: 2.29; 95% CI: 1.40-3.76; p = 0.001). Conclusions: Our results suggest that NPAS2 polymorphisms may serve as an independent prognostic marker for NSCLC patients.