Zhang Jian, Li Baosheng, Ding Xiuping, Sun Mingping, Li Hongsheng, Yang Ming, Zhou Changchun, Yu Haiying, Liu Hong, Yu Gongqi
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.
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.
Radiother Oncol. 2014 May;111(2):194-8. doi: 10.1016/j.radonc.2014.03.001. Epub 2014 Apr 17.
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.
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.
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.
Our results demonstrate that genetic variants of NOS2 may serve as a reliable predictor of RILI in lung cancer patients treated with thoracic radiation.
一氧化氮（NO）主要在病理条件下由诱导型一氧化氮合酶（NOS2）合成，在细胞毒性、炎症和纤维化中起重要作用。据报道，胸部放疗后呼出的NO升高可预测放射性肺损伤（RILI）。本研究探讨NOS2基因的遗传变异是否与RILI风险相关。
2009年至2011年间的301例患者队列，通过Sequenom MassArray系统对NOS2基因中的21个单核苷酸多态性（SNP）进行基因分型。采用Kaplan-Meier累积概率评估RILI风险，并进行Cox比例风险分析以评估NOS2基因型对RILI的影响。
多变量分析发现，在调整其他协变量后，NOS2基因中的三个SNP（rs2297518、rs1137933和rs16949）与RILI≥2的风险显著相关（P值分别为0.001、0.000092、0.001）。它们的关联独立于辐射剂量和平均肺剂量。进一步的单倍型分析表明，这三个SNP的ATC单倍型与降低发生RILI的风险相关。
我们的结果表明，NOS2的基因变异可能是接受胸部放疗的肺癌患者发生RILI的可靠预测指标。
