谷胱甘肽S-转移酶P1基因多态性与晚期胃癌奥沙利铂联合卡培他滨方案化疗疗效的关系  

Association between genetic polymorphisms of glutathione S-transferase P1 and clinical outcomes of oxaliplatin plus capecitabine chemotherapy in patients with metastatic gastric cancer

作　　者：董宁宁[1] 韩磊[2] DONG Ningning;HAN Lei(Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University/National Clinical Research Center of Gastrointestinal Disease/Beijing Digestive Disease Center/Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases,Beijing 100050,China;Department of Oncology,Affiliated Hospital of Jining Medical University,Shandong Jining 272000,China)

机构地区：[1]首都医科大学附属北京友谊医院消化分中心/国家消化系统疾病临床医学研究中心/北京市消化疾病中心/消化疾病癌前病变北京市重点实验室,北京100050 [2]济宁医学院附属医院肿瘤科,山东济宁272000

出　　处：《现代肿瘤医学》2023年第24期4572-4575,共4页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82070575);北京市优秀人才培养资助计划(编号:2015000021469G232)。

摘　　要：目的:探讨谷胱甘肽S-转移酶P1(glutathione S-transferase P1,GSTP1)rs1695基因多态性与晚期胃癌奥沙利铂联合卡培他滨方案(XELOX方案)化疗疗效的相关性。方法:回顾性选择102例晚期胃癌患者,均接受XELOX方案化疗,通过基质辅助激光解吸电离飞行时间(matrix-assisted laser desorption/ionization time-of-flight,MALDI-TOF)的方法明确GSTP1 rs1695基因分型,分析患者临床病理特征(包括年龄、性别、肿瘤分化程度、部位、ECOG-PS评分、TNM分期)及GSTP1 rs1695基因分型对患者化疗客观有效率(objective response rate,ORR)及疾病进展时间(progression-free survival,PFS)的影响。结果:102例患者中,GSTP1 rs1695 AA基因型、AG基因型、GG基因型所占例数分别为73例(71.6%)、27例(26.5%)、2例(2.0%),携带变异基因型GG/AG化疗ORR高于野生基因型AA(69.0%vs 43.8%,P=0.022),且携带变异基因型GG/AG患者PFS比野生基因型AA更长[6.1个月(95%CI:5.2~7.0)vs 5.1个月(95%CI:4.6~5.6),P=0.028]。患者临床病理特征均与化疗疗效无关,但肿瘤分化程度及TNM分期与PFS有关(P均<0.05)。Cox回归显示,肿瘤分化程度、TNM分期及GSTP1 rs1695是影响PFS的独立因素。结论:GSTP1 rs1695基因型与晚期胃癌患者XELOX方案化疗疗效密切相关,测定GSTP1 rs1695基因型可以为晚期胃癌的个体化治疗提供参考。Objective:To analyze the association between genetic polymorphisms of glutathione S-transferase P1(GSTP1)rs1695 and clinical outcomes of oxaliplatin plus capecitabine chemotherapy in patients with metastatic gastric cancer.Methods:102 patients with metastatic gastric cancer were enrolled.They received oxaliplatin in combination with capecitabine chemotherapy(XELOX regimen).GSTP1 rs1695 genotype was detected by matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF).The relationship between clinicopathological characteristics(including age,gender,tumor differentiation,location,Eastern Cooperative Oncology Group performance status,and TNM stage)and GSTP1 rs1695 genotypes and clinical outcomes[including objective response rate(ORR)and progression-free survival(PFS)]was analyzed.Results:Among these enrolled patients,73 patients(71.6%)carried GSTP1 rs1695 AA genotype,27 patients(26.5%)AG genotype,and 2 patients(2.0%)GG genotype.Patients harboring GG/AG genotype had both a statistically higher objective response rate than those with AA genotype(69.0%vs 43.8%,P=0.022),and longer progression-free survival[6.1 months(95%CI:5.2~7.0)vs 5.1 months(95%CI:4.6~5.6),P=0.028].None of the clinicopathological characteristics was related to tumor response,whereas,tumor differentiation and TNM stage were associated with progression-free survival(P<0.05).Cox regression analysis suggested that tumor differentiation,TNM stage and GSTP1 rs1695 were independent prognostic factors of progression-free survival.Conclusion:GSTP1 rs1695 genotype is closely related to the clinical outcomes of oxaliplatin plus capecitabine chemotherapy in patients with metastatic gastric cancer,which represents a further step towards individualized therapy.

关 键 词：晚期胃癌 谷胱甘肽S-转移酶P1 单核苷酸多态性 药物治疗 

分 类 号：R735.2[医药卫生—肿瘤]