晚期结直肠癌GSTP1基因多态性与奥沙利铂化疗效果关系

THE RELATIONSHIP BETWEEN THE GENETIC POLYMORPHISM OF GSTP1 AND THE CHEMOTHERAPEUTIC EFFECT OF OXALIPLATIN IN PATIENTS WITH ADVANCED COLORECTAL CANCER

目的探讨谷胱甘肽S转移酶P1(GSTP1)基因Ile105Val(A→G)多态性与晚期结直肠癌对以奥沙利铂为主方案化疗效果的关系。方法Ⅳ期结直肠癌病人102例,化疗前取静脉血应用TaqMan-MGB探针等位基因分型技术检测GSTP1基因Ile105Val的多态性。给予病人以奥沙利铂为主的方案化疗,2～3个周期后进行临床疗效评价并统计疾病进展时间(TTP),分析GSTP1基因型与化疗敏感性及生存期的关系。结果102例晚期结直肠癌病人中,A/A基因型54例(52.94%),G/G基因型10例(9.80%),G/A基因型38例(37.25%)。G/G+G/A基因型病人的化疗有效率为62.5%,A/A基因型病人的化疗有效率为25.9%,两者之间差异有显著性(χ2=14.21,P<0.01;OR=4.741,95%CI=1.556～13.207)。102例病人中位TTP为7.9个月,G/G+G/A基因型为9.7个月,A/A基因型为6.4个月,两者比较差异有显著性(χ2=35.001,P<0.01)。结论GSTP1 Ile105Val基因多态性可能与晚期结直肠癌病人对奥沙利铂化疗的敏感性及生存时间相关。

Objective To investigate the association of genetic polymorphisms of GSTP1 Ile105Val （A→G） with the outcome of oxaliplatin-based chemotherapy for patients with advanced coiorectal cancer. Methods This study consisted of 102 patients with stage-Ⅳ colorectal cancer. DNA of each patient was extracted from peripheral venous blood before the chemotherapy. GSTP1 genotypes were detected by TaqMan-MGB probe methods. The clinical response was evaluated after two to three cycles of therapy and the time to progress （TTP） evaiuated i and the relationship between GSTPI genotypes and chemotherapeutic sensitivity as well as survival analyzed. Results A/A genotype was found in 54 patients （52. 94%）, G/G genotype in 10 （9.80%） and G/A genotype in 38 （37.25 % ）. Patients possessing the G/G＋G/A genotype showed a chemotherapeutic efficiency of 62.5 % compared tO patients of A/A genotype of 25.9 % （χ^2= 14.21, P〈0.01 ;OR=4. 741,95% CI= 1. 556-13. 207）. The median TTP was 7.9 months for all the 102 patients; 9.7 months for G/G and G/A genotype, and 6.4 months for A/A. The differences among them were significant （χ^2=35. 001,P〈0.01）. Conclusion The GSTP1 Ile105Val polymorphism might be associated with the clinical responses and survival in patients with advanced colorectal cancer receiving oxaliplatin-based chemotherapy.