尿苷二磷酸葡糖苷酸转移酶1A1基因多态性与伊立替康不良反应的研究

Uridine diphosphate glucuronosyltransferase 1A1 gene polymorphism and irinotecan adverse reacrions investigation

目的探讨中国恶性肿瘤患者尿苷二磷酸葡糖苷酸转移酶1A1（UGT1A1）基因多态性与伊立替康（CPT-11）化疗的不良反应的发生率和严重程度的关系。方法用聚合酶链反应（PCR）法扩增目的基因片段，采用直接测序法分析UGT1A1基因多态性，检测2011年3月至2015年5月在我院住院治疗的439例恶性肿瘤患者UGT1A1基因多态性的分布情况，并对接受CPT-11治疗的128例患者毒性反应进行观察，比较不同基因型患者接受CPT-11治疗后不良反应发生率的差异。结果439例恶性肿瘤患者中UGT1A1基因纯合野生型TA6／6野生基因型343例（78．1％）；TA6／7杂合基因型84例（19．1％），TA7／7纯合基因型12例（2．8％）。128例接受CPT-11治疗的患者总体出现3～4度中性粒细胞减少12例（9．3％）；3～4度迟发性腹泻20例（15．6％）；基因型TA6／6、TA6／7之间比较，差异无统计学意义（P〉0．05）；TA7／7发生3～4级粒细胞减少及腹泻的比例明显增加。结论中国患者UGT1A1＋28多态性频率低，TA7／7纯合变异型患者应用CPT-11化疗发生Ⅲ度以上中性粒细胞减少和腹泻的风险增加，而TA6／7杂合子与TA6／6野生型相似，并不增加患者发生Ⅲ度以上中性粒细胞减少和腹泻的风险。

Objective Uridine diphosphate glucuronosyhransferase 1 A1 （UGT1A1） gene poly- morphism in Chinese patients with cancer and irinoteean （ CPT - 11 ） incidence of adverse reactions to chemotherapy and severity relationship. Methods The gene was amplified by polymerase chain reaction （PCR） fragment analysis UGT1A polymorphism by direct sequencing to detect from March 2011 to May 2015 in 439 eases of cancer patients in our hospital from UGT1 A1 gene polymorphism distribution, and toxicity in patients receiving 128 cases of CPT - 11 treatment were observed to compare different genotype differences in patients receiving CPT - 11 treatment after the incidence of adverse reactions. Results 439 cases of cancer patients in the UGT1A1 gene homozygous wildtype TA6/6 wild genotype 343 cases （78.1%）; TA6/7 heterozygous genotype 84 cases （19. 1% ）, TA7/7 genotype homozygous 12 cases （2. 8% ）. 128 cases receiving CPT - 11 treated patients generally appear 3 to 4 degrees neutropenia in 12 patients （9.3%） ; 3 to 4 degrees delayed diarrhea 20 cases （15.6%） ; there was no significant difference in TA6/6 and TA6/7 （ P 〉 0. 05 ） ; TA7/7 generation stage 3 - 4 nentropenia and diarrhea was significantly increased. Conclusion Chinese patients with UGT1A1 ＊ 28 polymorphism frequency is low, TA7/7 patients with homozygous mutant CPT - 11 chemotherapy to reduce the occurrence of the above m neutropenia and an increased risk of diarrhea, while TA6/7 heterozygotes and TA6/6 wild - type similar to patients does not increase above Ⅲ degree of risk of neutropenia and diarrhea. But whether patients need to choose the appropriate CPT - 11 through genetic screening, is worthy of further study.