目的 观察细胞色素P4502E1 的基因多态性对多西他赛联合卡培他滨方案一线治疗复发性乳腺癌疗效的影 响。方法 入选70 例手术后、辅助治疗后复发的乳腺癌患者,接受多西他赛联合卡培他滨方案一线化疗,同时检测 P4502E1 等位基因位点rs2070673 的单核苷酸多态性,比较不同基因型患者对治疗的反应率及预后的相关性进行分析。结 果 与P4502E1 基因的野生纯合子(AA 基因型)相比,杂合子(AT 基因型)降低了73% 的疾病进展风险(OR=0.27, 95CI=0.05~1.41),而突变纯合子(TT 基因型)更是将疾病进展风险降低了88%(OR=0.12,95%CI=0.02~0.71)。 P4502E1 基因为AA 基因型和AT 基因型的复发乳腺癌患者中位生存期为20.7 个月(95%CI=17.0~24.4),而 TT 基因型患 者的中位生存期明显长于AA 和 AT 基因型,为28.5 个月(95%CI=17.0~40.0),差别有统计学意义(P < 0.05)。结论 对于复发乳腺癌患者,细胞色素P4502E1 基因是可以影响多西他赛联合卡培他滨方案一线化疗疗效的多态性位点,TT 基 因型患者复发风险低且在生存期方面具有显著优势。为乳腺癌更为精准的个体化治疗提供了药物基因组学方面的参考。
Objective To investigate the association between cytochrome P4502E1 polymorphism and clinical outcomes in recurrent breast cancer patients treated by docetaxel plus capecitabine. Methods Seventy recurrent breast cancer patients who were treated with docetaxel plus capecitabine were included in this study. Meanwhile, the correlation between single nucleotide polymorphisms (SNP) sites at rs2070673 of CYP4502E1 alleles and treatment response rate and prognosis were analyzed. Results Compared with wild homozygote (AA genotype) of P4502E1 gene, heterozygote (AT genotype) reduced disease progression risk by 73% (OR=0.27, 95% CI=0.05~1.41), and mutated homozygote (TT genotype) reduced disease progression risk by 88% (OR=0.12, 95% CI=0.02~0.71). The median OS with AA and AT genotype was 20.7 months (95% CI=17.0~24.4), but the median OS of TT genotype was significantly longer 28.5 months (95% CI=17.0~40.0). There were statistically significant differences (P<0.05). Conclusion For patients with recurrent breast cancer, cytochrome P4502E1 gene is a polymorphic site that can affect the efficacy of first-line chemotherapy with docetaxel plus capecitabine. TT genotype patients have lower recurrence risk and significant advantage in survival. The P4502E1 gene is a polymorphic site that can affect the survival of patients with recurrent breast cancer treated by docetaxel plus capecitabine.