GSTP1基因多态性与结直肠癌患者奥沙利铂化疗敏感性及周围神经毒性的关系  

The correlation of GSTP1 polymorphism with oxaliplatin sensitivity and peripheral neurotoxicity in colorectal cancer patients

作　　者：曲珍 徐圣秋 王轩 QU Zhen;XU Shengqiu;WANG Xuan(Department of Pharmacy,Xuzhou First People's Hospital,Xuzhou,221100,Jiangsu,China;Department of Neurosurgery,Xuzhou First People's Hospital,Xuzhou,221100,Jiangsu,China)

机构地区：[1]徐州市第一人民医院药学部,江苏徐州221100 [2]徐州市第一人民医院神经外科,江苏徐州221100

出　　处：《肿瘤药学》2023年第4期449-454,共6页Anti-Tumor Pharmacy

基　　金：徐州市第一人民医院“青苗工程”——中青年医学人才培育计划(QMHB2021025);江苏省药学会—奥赛康医院药学科研项目(A202141);2020年中国矿业大学中央高校基本科研业务费资助项目青年科技基金(第二批)(2020QN91)。

摘　　要：目的探讨谷胱甘肽S-转移酶P1(GSTP1)基因多态性与结直肠癌患者含奥沙利铂化疗方案的敏感性及周围神经毒性(CIPN)的关系。方法选取某医院应用奥沙利铂化疗的结直肠癌患者70例,入院后24 h内统计患者基本临床资料。所有患者于化疗前静脉采血2 mL,采用地高辛原位杂交试剂盒进行杂交染色,多通道荧光定量分析仪检测GSTP1基因型,对比不同基因型患者化疗2个周期后的疗效及毒副反应发生情况。所有患者均经mFOLFOX6/XELOX方案治疗,采用实体瘤疗效评价标准(RECIST)进行疗效评价,美国国家癌症研究所常见不良反应术语评定标准(NCI-CTCAE)进行毒副反应评估。结果(1)患者性别、年龄、TNM分期、淋巴结转移情况、肿瘤部位、ECOG评分、化疗方案、伴发慢性病、奥沙利铂剂量等病理生理及药物因素与GSTP1基因型分布及化疗疗效无明显相关性(P>0.05)。(2)CIPN具有剂量累积性,奥沙利铂累积剂量高者CIPN发生率较高(P<0.05)。(3)GSTP1野生型与突变型患者疾病控制率分别为78.05%、89.66%,差异无统计学意义(P>0.05)。(4)GSTP1野生型患者CIPN、骨髓抑制发生率明显高于突变型患者(P<0.05),其余不良反应(乏力、胃肠道反应、口腔黏膜炎等)各基因型间的差异无统计学意义(P>0.05)。(5)70例患者CIPN发生程度较轻,无4级以上CIPN。GSTP1基因多态性与CIPN严重程度无关(P>0.05)。结论GSTP1基因多态性与结直肠癌患者病理生理因素、化疗疗效无关,与患者使用奥沙利铂后CIPN的发生相关。检测GSTP1基因多态性可能成为接受奥沙利铂化疗的结直肠癌患者发生CIPN的一个预测指标。Objective To investigate the correlation between the polymorphism of glutathione S-transferase P1(GSTPL)and the sensitivity and chemotherapy-induced peripheral neuropathy(CIPN)of oxaliplatin chemotherapy in advanced colorectal cancer.Methods A total of 70 patients with colorectal cancer treated with oxaliplatin in a hospital were selected.The basic clinical data of the patients were collected within 24 hours after admission.Blood samples(2 mL)were collected from all patients.The GSTP1 genotypes were detected by digoxin in situ hybridization kit and multi-channel fluorescence quantitative analysis.All patients were treated with mFOLFOX6/XELOX regimen.After two cycles of chemotherapy,the efficacy and toxicity were compared between patients with different genotypes.The efficacy was evaluated by the response evaluation criteria in solid tumor(RECIST),and the toxicity and side effects were evaluated by the USA National Cancer Institute common terminology criteria for adverse events(NCI-CTCAE).Results(1)There was no significant correlation between GSTP1 genotype and response to chemotherapy and other pathophysiological factors,such as gender,age,TNM stage,lymph node metastasis,tumor location,ECOG score,chemotherapy regimen,chronic disease,oxaliplatin dose and so on(P>0.05).(2)The incidence of CIPN was increased in the patients with high cumulative dose of oxaliplatin(P<0.05).(3)The control rates of patients with wild type and mutant type of GSTP1 were 78.05%and 89.66%,respectively,with no significant difference(P>0.05).(4)The incidence of CIPN and bone marrow suppression of GSTP1 wild-type patients were significantly higher than that of GSTP1 mutant patients(P<0.05).There was no significant difference in other adverse reactions(fatigue,gastrointestinal reaction,oral mucositis,etc)between patients with different genotypes(P>0.05).(5)The CIPN occurred was mild in 70 patients,and no grade 4 or above CIPN was found.The polymorphism of GSTP1 was not associated with the severity of CIPN(P>0.05).Conclusion The polymorphism of

关 键 词：结直肠癌 奥沙利铂 GSTP1基因多态性 疗效 周围神经毒性 

分 类 号：R735.3[医药卫生—肿瘤]