Jian Zhang1, Baosheng Li2, Xiuping Ding3, Mingping Sun3, Hongsheng Li3, Ming Yang4, Changchun Zhou3, Haiying Yu5, Hong Liu6, Gongqi Yu6. 1. Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, PR China; Shandong's Key Laboratory of Radiation Oncology, Jinan, PR China; Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, PR China. 2. Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, PR China; Shandong's Key Laboratory of Radiation Oncology, Jinan, PR China. Electronic address: baoshli@yahoo.com. 3. Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, PR China; Shandong's Key Laboratory of Radiation Oncology, Jinan, PR China. 4. College of Life Science and Technology, Beijing University of Chemical Technology, PR China. 5. Department of Radiology, Shandong Cancer Hospital, Jinan, PR China. 6. Shandong Provincial Institute of Dermatology and Venereology, Jinan, PR China.
Abstract
BACKGROUND AND PURPOSE: Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic radiation have been reported to predict radiation-induced lung injury (RILI). This study examined whether genetic variations in NOS2 gene is associated with the risk of RILI. MATERIAL AND METHODS: A cohort of 301 patients between 2009 and 2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2 gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was used to assess RILI risk and Cox proportional hazards analyses were performed to evaluate the effect of NOS2 genotypes on RILI. RESULTS: Multivariate analysis found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were significantly associated with risk of RILI⩾2 (P value=0.001, 0.000092, 0.001, respectively) after adjusting for other covariates. Their associations were independent of radiation dose and mean lung dose. Further haplotype analysis indicated that the ATC haplotype of three SNPs is associated with reducing the risk of developing RILI. CONCLUSION: Our results demonstrate that genetic variants of NOS2 may serve as a reliable predictor of RILI in lung cancer patients treated with thoracic radiation.
BACKGROUND AND PURPOSE:Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic radiation have been reported to predict radiation-induced lung injury (RILI). This study examined whether genetic variations in NOS2 gene is associated with the risk of RILI. MATERIAL AND METHODS: A cohort of 301 patients between 2009 and 2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2 gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was used to assess RILI risk and Cox proportional hazards analyses were performed to evaluate the effect of NOS2 genotypes on RILI. RESULTS: Multivariate analysis found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were significantly associated with risk of RILI⩾2 (P value=0.001, 0.000092, 0.001, respectively) after adjusting for other covariates. Their associations were independent of radiation dose and mean lung dose. Further haplotype analysis indicated that the ATC haplotype of three SNPs is associated with reducing the risk of developing RILI. CONCLUSION: Our results demonstrate that genetic variants of NOS2 may serve as a reliable predictor of RILI in lung cancerpatients treated with thoracic radiation.
Authors: Jamaji C Nwanaji-Enwerem; Marie-Abele Bind; Lingzhen Dai; Youssef Oulhote; Elena Colicino; Qian Di; Allan C Just; Lifang Hou; Pantel Vokonas; Brent A Coull; Marc G Weisskopf; Andrea A Baccarelli; Joel D Schwartz Journal: Toxicol Sci Date: 2017-07-01 Impact factor: 4.849
Authors: Abbas Salihi; Mohammed A Al-Naqshabandi; Zhikal Omar Khudhur; Zjwan Housein; Harmand A Hama; Ramyar M Abdullah; Bashdar Mahmud Hussen; Twana Alkasalias Journal: Mol Med Rep Date: 2022-05-26 Impact factor: 3.423