Geng Ruixuan, Chen Zhiyu, Zhao Xiaoying, Qiu Lixin, Liu Xin, Liu Rujiao, Guo Weijian, He Guang, Li Jin, Zhu Xiaodong
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
PLoS One. 2014 Dec 29;9(12):e116027. doi: 10.1371/journal.pone.0116027. eCollection 2014.
Oxidative stress genes are related to cancer development and treatment response. In this study, we aimed to determine the predictive and prognostic roles of oxidative stress-related genetic polymorphisms in metastatic gastric cancer (MGC) patients treated with chemotherapy.
In this retrospective study, we genotyped nine oxidative stress-related single nucleotide polymorphisms (SNPs) in NQO1, SOD2, SOD3, PON1, GSTP1, GSTT1, and NOS3 (rs1800566, rs10517, rs4880, rs1799895, rs662, rs854560, rs1695, rs2266637, rs1799983, respectively) in 108 consecutive MGC patients treated with epirubicin, oxaliplatin, and 5-fluorouracil (EOF) regimen as the first-line chemotherapy and analyzed the association between the genotypes and the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
We found that, in addition to a lower pathological grade (p = 0.017), NQO1 rs1800566 CT/TT genotype was an independent predictive factor of poor PFS (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.23-3.16; p = 0.005). PON1 rs662 AA/AG genotype was significantly associated with poor OS (HR = 1.95, 95% CI = 1.07-3.54; p = 0.029). No associations were detected between the nine SNPs and DCR.
NQO1 rs1800566 is an independent predictive factor of PFS for MGC patients treated with EOF chemotherapy, and PON1 rs662 is a noteworthy prognostic factor of OS. Information on oxidative stress-related genetic variants may facilitate optimization of individualized chemotherapy in clinical practice.
氧化应激基因与癌症的发生发展及治疗反应相关。在本研究中，我们旨在确定氧化应激相关基因多态性在接受化疗的转移性胃癌（MGC）患者中的预测和预后作用。
在这项回顾性研究中，我们对108例连续接受表柔比星、奥沙利铂和5-氟尿嘧啶（EOF）方案一线化疗的MGC患者的NQO1、SOD2、SOD3、PON1、GSTP1、GSTT1和NOS3基因中的9个氧化应激相关单核苷酸多态性（SNP）进行基因分型（分别为rs1800566、rs10517、rs4880、rs1799895、rs662、rs854560、rs1695、rs2266637、rs1799983），并分析基因型与疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）之间的关联。
我们发现，除了较低的病理分级（p = 0.017）外，NQO1 rs1800566 CT/TT基因型是PFS较差的独立预测因素（风险比[HR] = 1.97，95%置信区间[CI] = 1.23 - 3.16；p = 0.005）。PON1 rs662 AA/AG基因型与较差的OS显著相关（HR = 1.95，95% CI = 1.07 - 3.54；p = 0.029）。未检测到9个SNP与DCR之间的关联。
NQO1 rs1800566是接受EOF化疗的MGC患者PFS的独立预测因素，而PON1 rs662是值得关注的OS预后因素。氧化应激相关基因变异的信息可能有助于临床实践中个体化化疗的优化。
