GSTP1基因多态性与直肠癌化疗短期疗效及毒副反应的关系

Relationship between GSTP1 gene polymorphism and short-term efficacy and toxicity after rectal cancer chemotherapy

目的探讨谷胱甘肽S-转移酶P1(GSTP1)基因多态性与直肠癌化疗后短期疗效及毒副反应的关系。方法纳入2012年1月至2017年12月接受一线化疗的167例晚期直肠癌患者,采集化疗前静脉血,采用基质辅助激光解吸电离飞行时间质谱法检测GSTP1 rs1695基因型,对比野生型与突变型患者化疗2个周期后疗效及毒副反应发生情况。结果 167例患者中,纯合野生型(AA型) 113例、杂合突变型(AG型) 47例、纯合突变型(GG型) 7例。对接受以奥沙利铂为主方案化疗的87例患者,突变型患者完全缓解(CR)、部分缓解(PR)、稳定(SD)、进展(PD)者各0、17、6、3例,野生型患者各0、23、20、18例,两组对比,差异有统计学意义(P<0.05)。对接受以伊利替康为主方案化疗的80例患者,突变型患者CR、PR、SD、PD者各0、11、8、9例,野生型患者各0、21、16、15例,两组对比,差异无统计学意义(P>0.05)。两种化疗方案中,突变型患者与野生型患者Ⅲ～Ⅳ度毒副反应对比,差异均无统计学意义(P>0.05)。结论 GSTP1基因rs1695位点发生A>G突变,可提升奥沙利铂为主化疗方案对晚期直肠癌一线化疗的短期疗效,但不会影响伊利替康为主化疗方案的短期疗效。

Objective To investigate the relationship between glutathione S-transferase P1 GSTP1 gene polymorphism and short-term efficacy and toxicity of chemotherapy for rectal cancer.Methods 167 patients with advanced rectal cancer who received first-line chemotherapy from January 2012 to December 2017 were enrolled in this study.Venous blood samples were collected before chemotherapy.GSTP1 rs1695 genotype was detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.The efficacy and toxicity and side effects of wild type and mutant type patients after 2 cycles of chemotherapy were compared.Results Among the 167 patients 113 were homozygous wild type AA type 47 were heterozygous mutant AG type and 7 were homozygous mutant GG type.Among 87 patients receiving oxaliplatin-based chemotherapy Complete remission CR partial remission PR stability SD and progression PD were 0 17 6 and 3 in mutant patients and 0 23 20 and 18 in wild type patients the short-term efficacy of mutant-type patients was significantly better than that of wild-type patients P<0.05.Among 80 patients receiving irinotecan-based chemotherapy CR PR SD and PD were 0 11 8 and 9 cases in mutant patients and 0 21 16 and 15 cases in wild type patients respectively there was no significant difference in the short-term efficacy between the mutant-type patients and the wild-type patients P >0.05.Among patients receive either chemotherapy there was no significant difference in the Grade Ⅲ and Ⅳ toxicity between the mutant-type patients and the wild-type patients P >0.05.Conclusion A >G mutation at rs1695 of GSTP1 gene can enhance the short-term efficacy of oxaliplatin-based chemotherapy for advanced rectal cancer but it will not affect the short-term efficy of irinotecan-based chemotherapy.