GSTP1、MTHFR基因多态性与PF方案治疗食管癌疗效相关性研究

Genetic polymorphism of GSTP1,MTHFR correlated with response to cisplatin and fluorouracil chemotherapy in esophagus cancer

目的：了解食管癌患者谷胱甘肽S转移酶P1（glutathione S-transferase Pi-1,GSTP1）,亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因多态性分布频率,探讨GSTP1、MTHFR基因多态性与食管癌患者PF方案（顺铂联合5-氟尿嘧啶）化疗疗效相关性。方法：从168例接受PF方案化疗的食管癌病例中采外周血提取DNA,采用PCR法扩增目的基因片段,直接测序法分析GSTP1、MTHFR基因多态性,每两周期化疗后评价疗效一次,按照实体瘤的疗效评价标准进行评价。结果：168例食管癌患者PF方案化疗疗效评价（实体瘤的疗效评价标准RECIST 3.0）,CR 19例（11.3%）,PR 60例（35.7%）,SD 48例（28.6%）,PD 41例（24.4）,食管癌患者GSTP1基因野生型（AA）有效率为22.0%,杂合型（AG）＋纯合型（GG）有效率为25.0%,MTHFR C667T基因野生型（CC）有效率为14.3%,杂合型（CT）＋纯合型（TT）有效率为32.7%,MTHFR A1298C基因野生型（AA）有效率为17.3%,杂合型（AC）＋纯合型（CC）有效率为29.8%,其中GSTP1基因野生型（AA）与杂合型（AG）＋纯合型（GG）的OR=2.520,95%CI：11.237-25.191,P=0.012,MTHFR C6 6 7 T基因野生型（CC）与杂合型（CT）＋纯合型（TT）的OR=1.933,95%CI：5.987-16.354,P=0.032,MTHFR A1298C基因野生型（AA）与杂合型（AC）＋纯合型（CC）的OR=3.514,95%CI：19.018-27.332,P=0.511。结果显示食管癌患者GSTP1基因及MTHFR C667T基因多态性与PF方案化疗后疗效相关,且杂合型及纯合型疗效优于野生型。结论：GSTP1及MTHFR-C677T基因多态性与5-氟尿嘧啶的疗效具有相关性,而MTHFR-A1298C基因多态性与5-氟尿嘧啶的疗效无明显相关性,故检测GSTP1及MTHFR-C677T基因多态性可预测PF方案化疗疗效。

Objective： To detect the polymorphism of GSTP1,MTHFR distribution frequency,and investigate the association of the genetic polymorphism of GSTP1,MTHFR with response to cisplatin and fluorouracil chemotherapy in Esophagus cancer. Methods： To select 168 of esophageal cancer patients who underwent PF（ cisplatin plus 5- fluorouracil） chemotherapy to test peripheral blood DNA,gene fragment amplified by PCR method. By using direct sequencing method to examine GSTP1 and MTHFR gene polymorphism. Results： In 168 esophageal cancer patients treated with chemotherapy,curative effect of PF scheme（ solid tumor curative effect evaluation standard RECIST 3. 0）,CR 19 cases（ 11. 3%）,PR 60 cases（ 35. 7%）,SD 48 cases（ 28. 6%）,PD 41 cases（ 24. 4）. In esophageal GSTP1 wild type gene patients with（ AA） effective rate was 22. 0%,hybrid type（ AG） ＋ homozygous type（ GG） effective rate25. 0%. MTHFR C667 T wild type gene（ CC） effective rate was 14. 3%,the hybrid type（ CT） ＋（ TT） homozygous type effective rate was 32. 7%,MTHFR A1298 C wild type gene（ AA） effective rate was 17. 3%,hybrid type（ AC） ＋ homozygous type（ CC） effective rate was 29. 8%,including GSTP1 wild- type genotype（ AA） and hybrid（ AG） ＋（ GG） homozygous type OR = 2. 520,95% CI： 11. 237 - 25. 191,P = 0. 012,MTHFR C667 T wild- type genotype（ CC） and hybrid（ CT） ＋（ TT） homozygous type OR = 1. 933,95% CI： 5. 987 - 16. 354,P = 0. 032,MTHFR A1298 C wild- type genotype（ AA） and hybrid type（ AC） ＋ homozygous CC OR = 3. 514,95% CI： 19. 018 - 27. 332,P =0. 511. Results showed that patients with esophageal GSTP1 gene and MTHFR C667 T gene polymorphism was associated with PF scheme after chemotherapy curative effect,and hybrid type and homozygous type curative effect was better than the wild type. Conclusion： GSTP1 and MTHFR gene C677 T polymorphism associated with the curative effect of 5- fluorouracil. MTHFR A1298 C genetic polymorphisms and the curative effect of 5- fluorouracil has no obvious correlation,so the detection of GSTP1 and MTHFR gene C677 T polymorphism- may predict PF chemotherapy curative effect.