浙江台州地区使用伊立替康人群UGT1A1基因多态性相关性研究

目的 研究浙江台州地区使用伊立替康（CPT-11）人群UGT1A1基因多态性和不良反应的相关性。方法 以使用含CPT-11化疗的132例台州地区汉族肿瘤患者为研究对象，取其外周血提取基因组DNA，进行UGT1A1基因多态性检测。结果 132例以CPT-11为基础化疗方案的台州地区肿瘤患者中UGT1A1*28 TA（6/6）野生型93例（70.45%），TA（6/7）杂合突变型共36例（27.27%），TA（7/7）纯合突变型仅3例（2.27%）；UGT1A1*6 G/G野生型共97例（73.48%），G/A杂合突变型共35例（26.52%），未找到A/A纯合突变型。UGT1A1*28非野生型（6/7+7/7）患者发生腹泻的概率显著高于野生型患者（P=0.040）。而粒细胞减少、血小板减少、血红蛋白减少与UGT1A1*28基因多态性无显著性差异。迟发性腹泻、粒细胞减少、血小板减少、血红蛋白减少水平与UGT1A1*6基因多态性无显著性差异。结论 浙江台州地区UGT1A1基因突变频率较高，TA（6/6）野生型人群相比TA（6/7）和TA（7/7），CPT-11使用后的腹泻风险增加。建议浙江台州地区肿瘤患者使用CPT-11化疗前进行UGT1A1基因多态性检测，以预测患者对CPT-11的耐受性，保证化疗的顺利进行。

Relevance Research of UGT1A1 Gene Polymorphism in Taizhou Area of Zhejiang Province Patients with Irinotecan Chemotherapy

OBJECTIVE To investigate UGT1A1 gene polymorphism and adverse relevance of irinotecan users in Taizhou, Zhejiang. METHODS Choose 132 Han nationality tumor patients treated with irinotecan-based chemotherapy in Taizhou. Take their peripheral blood to extract DNA for test of UGT1A1 gene polymorphism. RESULTS Among 132 cancer patients in Taizhou collected to detect UGT1A1 gene polymorphisms, the rates of wide type TA (6/6), heterozygous mutants TA(6/7), homozygous mutants TA(7/7) of UGT1A1*28 gene were 70.45%, 27.27%, 2.27%. The rates of UGT1A1*6 wide type G/G were 73.48% and heterozygous mutants of G/A were 26.52%. The incidence of diarrhea in UGT1A1*28 non-wild type patients (6/7+7/7) was significantly higher than that in wild type patients (P=0.040). There was no significant difference between UGT1A1*28 gene polymorphism and neutropenia, thrombocytopenia and hemoglobin reduction. There was no correlation between UGT1A1*6 gene polymorphism and delayed diarrhea, neutropenia, thrombocytopenia and hemoglobin reduction. CONCLUSION UGT1A1 has a high frequency in Taizhou, Zhejiang. To TA(6/7) and TA(7/7) throng, there are obviously more diarrhea after using irinotecan during TA(6/6) wild-type throng. The study suggests that lung and colorectal cancer patients in Taizhou, Zhejiang, should do the test of UGT1A1 gene promoter polymorphism before chemotherapy with irinotecan. It will assist predicting patients'' resistance so that it can adjust the dosage to help the smooth progress of chemotherapy.