UGT1 A1基因多态性与小细胞肺癌伊立替康化疗毒性和疗效的研究

目的：探讨中国人小细胞肺癌患者尿苷二磷酸葡糖苷酸转移酶1A1（ uridine diphosphate glucuronosyl transferase 1A1，UGT1A1）基因多态性分布与伊立替康（ irinotecan，CPT-11）化疗毒性和疗效的关系。方法接受CPT-11联合顺铂一线治疗的小细胞肺癌患者34例，外周血中提取DNA，PCR法扩增目的基因片段，直接测序法分析UGT1A1＊28基因多态性，并与不良反应及近期疗效进行分析。结果34例患者中UGT1A1＊28野生纯合型（ TA 6/6）最常见为26例（76.5%），其次为突变杂合型（TA 6/7）6例（17.6%）；突变纯合型（TA 7/7）仅2例（5.9%）， UGT1A1＊28非野生型可增加患者发生Ⅲ度以上腹泻的风险（ p ＜0.05）。结论中国人小细胞肺癌患者 UGT 1A1＊28突变频率低，TA 6/7和TA 7/7基因型可增加应用CPT-11后III度以上腹泻的风险，但不影响疗效。

CORRELATION BETWEEN UGT1 A1 GENE POLYMORPHISMS AND TOXICITY AND EFFICACY OF IRINOTECAN CHEMOTHERAPY ON SMALL CELL LUNG CANCER PATIENTS

OcjectiVe To observe the association of uridine diphosphate glucuronosyl transferase 1 A1（ UGT1 A1 ） gene polymorphism with the toXicity and toXicity of irinotecan（ CPT-11 ） chemotherapy in Chinese patients with small cell lung cancer（ SCLC ）. Methods In 34 patients with SCLC who had received first-line treatment with irinotecan plus cisplatin,genomic DNA samples were eXtracted,leukocytes in the peripheral blood,and the geno types were determined by analyzing the sequence of the UGT1A1 gene. The influence of the UGT1A1＊ 28 polymorphism on the short-term efficacy and toXicity of irinotecan was analyzed. Results The UGT1A1 genotypes in 34 consecutive patients were as follows：UGT1A1＊28 homozygous wild-type TA6/6（ 26 cases,76. 5%）,heterozygous mutant-type TA6/7（ 6 cases,17. 6%）,homozygous mutant-type TA7/7（ 2 cases,5. 9%）. Marked increases in diarrhea were observed in patients who had the TA 6/7 or TA 7/7 geno type（ p〈0 . 05 ）. Conclusion The polymorphism of UGTIAl＊28 in Chinese SCLC patients was lower,TA6/7 orTA7/7 increased the risk of developing grade or more severe diarrhea for the patients after receiving irinotecan treatment but had no influence on efficacy of chemotherapy.