尿苷二磷酸葡醛酰转移酶1A1基因多态性与伊立替康治疗广泛期小细胞肺癌不良反应的相关性

Association of UGTIA1 （＊28, ＊60 and ＊93） polymorphism with the adverse reactionsof irinotecan chemotherapy in extensive stage small cell lung cancer

目的研究尿苷二磷酸葡醛酰转移酶（UGT）1A1基因多态性与伊立替康方案治疗广泛期小细胞肺癌患者不良反应的关系。方法采用聚合酶链反应法扩增目的基因片段，直接测序法对UGT1A1基因多态性进行检测，观察并记录化疗中出现的不良反应及疗效，比较不同基因型患者使用伊立替康不良反应的发生率。结果58例广泛期小细胞肺癌患者中，UGT1A1＊28野生型45例（77．6％），UGT1A1＊93野生型40例（69．0％），UGT1A1＊60野生型38例（65．5％），UGT1A1＊93和UGT1A1＊60基因突变分别有18例（31．0％）和20例（34．5％）。UGT1A1＊28基因型中，TA5突变8例（13．8％），TA7突变5例（8．6％）。TA5突变型中／〉3级腹泻5例，≥3级白细胞和中性粒细胞减少各3例；UGT1A1＊93突变型中，≥3级腹泻7例，≥3级白细胞减少6例，I〉3级中性粒细胞减少4例。结论TA5突变型、UGTIAl＊93突变型均增加腹泻和I〉3级白细胞和中性粒细胞减少的风险，而UGT1A1（＊28、＊93、＊60）野生型和UGT1A1＊60突变型未增加药物不良反应的风险。

Objective To explore the correlation between UGT1A1 （ ＊ 28, ＊ 60 and ＊ 93） polymorphism and the adverse reactions in small cell lung cancer patients after irinotecan chemotherapy. Methods Clinical data of 58 small cell lung cancer patients in extensive stage treated in our hospital were retrospectively analyzed. Polymerase chain reaction was used to amplify the UTG, and direct sequencing was performed to determine the UGT polymorphism. The adverse reactions ≥ grade 3 after irinotecan chemotherapy in patients with different UGT genotype were analyzed. Results Amongthe 58 patients with extensive stage small cell lung cancer, there were 45（77.6% ）cases of wild type UGT1A1 ＊ 28, 40（69.0% ）cases of wild type UGT1A1 ＊93, 38 （65.5%） cases of wild type UGT1A1 ＊60, 18 cases of mutation in UGT1A1 ＊93 and 20 cases of mutation in UGT1A1 ＊ 60. In UGT1A1 promoter position 28, there were 8 （ 13.8% ） cases of TA5 mutation and 5 （8.6%） cases of TAT mutation. Among the patients with TA5 mutation, 5 cases had ≥grade 3 diarrhea, 3 cases had ≥grade 3 leucopenia and 3 cases had ≥grade 3 neutropenia, while among the patients with UGT1A1 ＊ 93 mutation, 7 cases had ≥grade 3 diarrhea, 6 cases had .--〉grade 3 leucopenia and 4 cases had I〉 grade 3 neutropenia. Conclusions TA5 and UGT1 A1 ＊ 93 mutation increase the risk of diarrhea and ≥grade 3 leukopenia and neutropenia, however, wild type UGT1A1 （ ＊ 28, ＊ 93, ＊ 60） and mutant UGT1A1 ＊ 60 do not increase those risks. Further prospective study in a larger number of patients is needed to clarify the association between UGT1A1 ＊ 28, UGT1A1 ＊ 93 and UGT1A1 ＊ 60 polymorphism and adverse reactions of irinotecan, and to help clinicians in choosing a better therapeutic modality for personalized chemotherapy to improve curative effect and reduce adverse reactions.