MDR1基因C3435T多态性对弥漫性大B细胞淋巴瘤化疗效果及血液学毒性的影响

摘要

Objective To explore the impact of multidrug resistance 1(MDR1) C3435T polymorphism on chemotherapy efficacy and hematologic toxicity in patients with diffuse large B-cell lymphoma( DLBCL) .Methods One hundred and seventeen DLBCL patients underwent initial treatment received 4 -8 cycles of CHOP ( cyclophosphamide, leurocristine, doxorubicin and prednisone ) or R-CHOP ( rituximab,cyclophosphamide,leurocristine,doxorubicin and prednisone) in a 21-day cycle as frontline chemotherapy.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to detect the patients′MDR1 C3435T polymorphism after they had received chemotherapy.The therapeutic response,survival time and hematological toxicity were compared among patients with different genotypes.Results There were 47 cases(40.2%) of genotype CC,17 cases(14.5%) of genotype TT and 53 cases(45.3%) of genotype CT among the 117 patients,the frequencies of allele C and T were 62.8%and 37.2%,respectively.The patients with genotype CT+TT gained longer median progression-free survival(PFS) as well as lower incidences of severe anemia and thrombocytopenia compared with the patients with genotype CC(all P<0.05).There was no significant difference in the overall remission rate,complete remission rate, overall survival time or incidence of leucocytopenia between patients with genotype CT+TT and genotype CC(all P>0.05).Conclusion MDR1 C3435T polymorphism might have an impact on the chemotherapy efficacy and hematologic toxicity in patients with DLBCL,and the patients with genotype CT+TT might have longer PFS and lower incidences of anemia and thrombocytopenia.%目的：探讨多药耐药MDR1基因C3435 T多态性对弥漫性大B细胞淋巴瘤（ DLBCL）患者化疗效果及血液学毒性的影响。方法117例初治DLBCL患者均采用环磷酰胺、长春新碱、阿霉素、泼尼松方案或利妥昔单抗、环磷酰胺、长春新碱、阿霉素、泼尼松方案化疗，21 d为1周期，化疗4～8周期。化疗后采用聚合酶链式反应－限制性片段长度多态性（PCR-RFLP）方法检测患者 MDR1基因 C3435T 多态性；比较不同基因型患者化疗疗效、生存时间及血液学毒性。结果117例患者中，检出CC基因型47例（40．2％），TT基因型17例（14．5％），CT基因型53例（45．3％），C和T等位基因频率分别是62．8％和37．2％。与CC基因型组比较，CT＋TT基因型组患者的中位无进展生存时间（ PFS）长、严重贫血和血小板减少发生率低（P均＜0．05），而两组患者化疗后总缓解率、完全缓解率、总生存时间、白细胞减少发生率差异无统计学意义（P均＞0．05）。结论 MDR1基因C3435T多态性可能影响DLBCL患者的化疗效果及血液学毒性，CC＋CT基因型患者的PFS长、发生贫血和血小板减少的可能性低。