CAJ | 학술논문

目的:研究应用伊立替康化学治疗(化疗)的进展期消化道肿瘤患者不良反应的发生率及严重程度与UGT1A1基因启动子区多态性的关系.方法:选择66例汉族进展期消化道肿瘤患者,使用含伊立替康的方案化疗,观察并记录患者化疗中出现的不良反应、化疗前总胆红素水平和化疗后至Ⅲ度以上严重毒性时间(周);外周血中抽提基因组DNA,测定UGT1A1基因启动子区TATA盒胸腺嘧啶-腺嘌呤(TA)序列重复次数,统计分析基因型与不良反应的关系,比较不同基因型患者化疗前总胆红素水平和至严重毒性时间的差异.结果:55例患者(83.3%)UGT1A1基因启动子区TA序列6次重复,为纯合野生型(TA)6/(TA)6(UGT1A1*1/*1);11例患者(16.70%)基因型为TA序列6次和7次重复的杂合(TA)6/(TA)7(UGT1A1*28/*1),未发现TA序列7次重复UGT1A1*28/*28的纯合突变.以上2组患者发生Ⅲ度以上白细胞或中性粒细胞减少者分别为26例和5例(47.3%比45.5%,P=1.000),发生Ⅲ度以上腹泻者分别为5例和4例(9.1%比36.4%,P=0.036).2组治疗前总胆红素水平分别为(15.1±1.1)μmol/L和(20.8±5.1)μmol/L(P=0.09),至严重毒性时间2组分别为9周和3周(P=0.186).结论:在应用伊立替康化疗的汉族患者中,UGT1A1启动子区TATA盒基冈多态性(TA)6/(TA)7杂合状态可以增加患者发生Ⅲ度以上腹泻的风险,但不会增加患者发生Ⅲ度以上白细胞或中性粒细胞减少的风险.
목적:연구응용이립체강화학치료(화료)적진전기소화도종류환자불량반응적발생솔급엄중정도여UGT1A1기인계동자구다태성적관계.방법:선택66례한족진전기소화도종류환자,사용함이립체강적방안화료,관찰병기록환자화료중출현적불량반응、화료전총담홍소수평화화료후지Ⅲ도이상엄중독성시간(주);외주혈중추제기인조DNA,측정UGT1A1기인계동자구TATA합흉선밀정-선표령(TA)서렬중복차수,통계분석기인형여불량반응적관계,비교불동기인형환자화료전총담홍소수평화지엄중독성시간적차이.결과:55례환자(83.3%)UGT1A1기인계동자구TA서렬6차중복,위순합야생형(TA)6/(TA)6(UGT1A1*1/*1);11례환자(16.70%)기인형위TA서렬6차화7차중복적잡합(TA)6/(TA)7(UGT1A1*28/*1),미발현TA서렬7차중복UGT1A1*28/*28적순합돌변.이상2조환자발생Ⅲ도이상백세포혹중성립세포감소자분별위26례화5례(47.3%비45.5%,P=1.000),발생Ⅲ도이상복사자분별위5례화4례(9.1%비36.4%,P=0.036).2조치료전총담홍소수평분별위(15.1±1.1)μmol/L화(20.8±5.1)μmol/L(P=0.09),지엄중독성시간2조분별위9주화3주(P=0.186).결론:재응용이립체강화료적한족환자중,UGT1A1계동자구TATA합기강다태성(TA)6/(TA)7잡합상태가이증가환자발생Ⅲ도이상복사적풍험,단불회증가환자발생Ⅲ도이상백세포혹중성립세포감소적풍험.
Objective To investigate the incidence and severity of adverse events in Han pateints with advanced digestive tumor treated with irinotecan-based chemotherapy, and their relationship with UGT1A1 gene promoter polymorphism. Methods Sixty-six advanced digestive tumor patients treated with irinotecan-based chemotherapy were enrolled, and the adverse events during chemotherapy, the pretreatment bilirubin level, and the time to the occurrence of degree Ⅲ toxicity were observed. Genomic DNA was extracted from peripheral blood to examine the frequency of UGT1A1 TATA box thymine-adenine (TA) repeats, and its relationship with adverse events was analyzed. The differences of the pretreatment bilirubin level and the time to the occurrence of severe toxicity were also compared. Results Fifty-five patients (83.3%) were identified with (TA)6/(TA)6 genotype, and eleven patients (16.7%) with UGT1A1*28/*1 polymorphism [thymine-adenine (TA)6/(TA)7 genotype, no (TA)7/(TA)7 genotype was found]. In the two groups, 26 and 5 patients (47.3% vs 45.5%,P=1.000) had grade 3 and 4 neutropenia and 5 and 4 patients (9.1% vs 36.4% ,P--0.036) had grade 3 and 4 diarrhea, respectively. The pretreatment bilirubin levels of the two groups were (15.1±1.1) μmol/L and (20.8±5.1) μmol/L, respectively (P=0.09). The time to occurrence of severe toxicity of the two groups were 9 weeks and 3 weeks of postchemotherapy, respectively (P=0.186). Conclusions The marked increase in grade 3 or 4 diarrhea, but not in grade 3 or 4 neutropenia may occur in patients treated with irinotecan-based chemotherapy who had (TA)6/(TA)7 genotype.