GSTP1和GSTM1基因多态性与卵巢浆液性腺癌患者生存的相关性分析  

GSTP1 and GSTM1 polymorphisms and survival in ovarian carcinoma treated with chemotherapy

作　　者：翟向红[1,2] 王岸聪[2] 

机构地区：[1]山东省临沂卫生学校妇产科教研室,山东临沂276002 [2]临沂市人民医院妇产科,山东临沂276002

出　　处：《中华肿瘤防治杂志》2015年第17期1388-1392,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的探讨谷胱甘肽孓转移酶P1（glutathione S-transferase Pl，GSTP1）和谷胱甘肽孓转移酶M1（glutathione S-transferaseM1，GSTM1）基因单核苷酸多态性对化疗治疗卵巢浆液性囊腺癌患者生存的影响。方法选取2004—08—31—2012-08—01就诊临沂市人民医院妇科的106例患者，应用紫杉醇联合卡铂（taxol＋carboplatin，TP）方案64例，其他化疗方案（拓扑替康、环磷酰胺、异环磷酰胺或吉西他滨）42例。应用焦磷酸测序法检测GSTP1和GSTM1的单核苷酸基因多态性（GSTP1 Ile105Val，GSTM1缺失型／GSTM1非缺失型）。基因型和总体生存率之间的关联使用Kaplan-Meier生存曲线和Cox比例风险回归模型进行评估。结果总生存率（overallsurvival，OS）比较结果显示，TP组患者总生存率为38．1％，显著高于其他化疗组的23．2％，Plog-rank=0．006。GSTP1（异亮氨酸纯合予，A／A）基因型患者总生存率为34．6％，GSTP1（异亮氨酸杂合子，A／G）总生存率为57．6％，差异无统计学意义，x^2=0．132，Plog-rank=0．716。Cox比例风险回归分析结果显示，GSTP1（A／G）与等住基因（A／A）风险系数比为1．20，95％CI为0．55～2．63，P=0．65。未检测到GSTP1缬氨酸等住基因纯合子载体（G／G）。GSTM1缺失型患者总生存率为29．5％，GSTM1非缺失型患者总生存率为74．9％，差异无统计学意义，x^2=0．015，Plog-rank旧。x^2=0．902。GSTM1基因无缺失型与缺失型Cox比例风险系数比为1．07，95％CI为0．48～2．42，P=0．87。结论不同GSTP1和GSTM1基因型患者化疗后总生存差异无统计学意义，但应用TP方案化疗患者总生存率显著高于其他方案化疗患者。OBJECTIVE The effects of platinum agents are controlled by genes involved in DNA detoxification[glu- tathione S-transferase P1（GSTP1） and glutathione S-transferase M1 （GSTM1）] which have been associated with increased chemotherapeutic treatment benefit in ovarian cancer patients. The study assessed the effect of single nucleotide polymor- phisms in GST genes on survival in ovarian serous cystadenocarcinoma women treated with chemotherapy. METHODS A total of 106 of the patients received treatment with carbplatin-based or else chemotherapy. Polymorphisms were genotyped by pyrosequencing （GSTP1 Ile105Val, null/non-null genotypes for GSTM1）. Associations between genotypes and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS The overall sur- vival （OS） of TP （taxol＋carboplatin） regimen was significantly longer than that of else chemotherapy （Plog-rank=0. 006）. Kaplan-Meier survivorship functions did not differ significantly by GSTP1 genotype （34. 6% vs 57.6%, x^2 = 0. 132, Plog rank =0. 716）. Cox proportional hazards regression revealed not significant association between the GSTP1 valine allele and risk of dying since treatment start, with HRs of 1.20 （95%CI：0. 55-2. 63; P=0.65） for heterozygous carriers of the valine allele and 0 for homozygous carriers of the valine allele. Kaplan-Meier survivorship functions did not differ significantly compared null genotype for GSTM1 with no-null genotype（29.5% vs 74.90%, x^2 =0. 015, Plog-rank =0. 902）. As compared with carrier of two copies of GSTM1, both individuals with one or no copy of GSTM1 present showed no decreased risk of dying after therapy with HRs of 1.07 （95% CI：0.48-2.42; P= 0.87）. CONCLUSION The results indicate that no associations between polymorphisms in GSTP1 and survival after adjuvant chemotherapy were observed, so as to GSTM1.

关 键 词：单核苷酸多态性 化学治疗 焦磷酸测序 卵巢浆液性囊腺癌 GSTM1 GSTP1 卡铂 遗传药理学 

分 类 号：R737.31[医药卫生—肿瘤]