中国药物应用与监测
中國藥物應用與鑑測
중국약물응용여감측
CHINESE JOURNAL OF DRUG APPLICATION AND MONITORING
2014年
5期
263-266
,共4页
张勇%苏丹%张婷婷%毛志远%白莉
張勇%囌丹%張婷婷%毛誌遠%白莉
장용%소단%장정정%모지원%백리
UGT1A1%基因多态性%伊立替康%结直肠肿瘤%中性粒细胞减少%迟发性腹泻
UGT1A1%基因多態性%伊立替康%結直腸腫瘤%中性粒細胞減少%遲髮性腹瀉
UGT1A1%기인다태성%이립체강%결직장종류%중성립세포감소%지발성복사
UGT1A1%Gene polymorphism%Irinotecan%Colorectal neoplasms%Neutropenia%Delayed diarrhea
目的：探讨UGT1A1*28/*6基因多态性与伊立替康治疗晚期结直肠癌的毒性和疗效的关系。方法：选取2011年6月-2013年6月在我科治疗的晚期结直肠癌患者，共计102例，对其进行UGT1A1*28/*6基因检测，随访记录患者行伊立替康化疗后的不良反应和近期疗效，比较不同基因型患者之间有无差异。结果：不同UGT1A1*28/*6基因型患者中3~4级中性粒细胞减少和迟发性腹泻发生率无显著差异。联合UGT1A1*28和*6两位点分析，野生型、单点变异型和双点变异型患者中3~4级中性粒细胞减少发生率逐渐升高，三者有显著差异且升高趋势有统计学意义（4.3%、17.4%、57.1%，P=0.005，趋势检验P =0.002）。UGT1A1*28基因型对治疗有效率（RR）和疾病控制率（DCR）无显著影响，但UGT1A1*6基因突变者较野生型者RR、DCR均明显降低（P=0.023，P=0.032）。联合两位点分析，野生型、单点变异型和双点变异型患者RR、DCR均有显著差异（P=0.002，P=0.008），且DCR降低趋势有统计学意义（95.7%、73.9%、42.9%，趋势检验P=0.001）。结论：在预测伊立替康毒性及疗效时，联合检测UGT1A1*28/*6两位点基因较单独检测一个位点更有价值。
目的：探討UGT1A1*28/*6基因多態性與伊立替康治療晚期結直腸癌的毒性和療效的關繫。方法：選取2011年6月-2013年6月在我科治療的晚期結直腸癌患者，共計102例，對其進行UGT1A1*28/*6基因檢測，隨訪記錄患者行伊立替康化療後的不良反應和近期療效，比較不同基因型患者之間有無差異。結果：不同UGT1A1*28/*6基因型患者中3~4級中性粒細胞減少和遲髮性腹瀉髮生率無顯著差異。聯閤UGT1A1*28和*6兩位點分析，野生型、單點變異型和雙點變異型患者中3~4級中性粒細胞減少髮生率逐漸升高，三者有顯著差異且升高趨勢有統計學意義（4.3%、17.4%、57.1%，P=0.005，趨勢檢驗P =0.002）。UGT1A1*28基因型對治療有效率（RR）和疾病控製率（DCR）無顯著影響，但UGT1A1*6基因突變者較野生型者RR、DCR均明顯降低（P=0.023，P=0.032）。聯閤兩位點分析，野生型、單點變異型和雙點變異型患者RR、DCR均有顯著差異（P=0.002，P=0.008），且DCR降低趨勢有統計學意義（95.7%、73.9%、42.9%，趨勢檢驗P=0.001）。結論：在預測伊立替康毒性及療效時，聯閤檢測UGT1A1*28/*6兩位點基因較單獨檢測一箇位點更有價值。
목적：탐토UGT1A1*28/*6기인다태성여이립체강치료만기결직장암적독성화료효적관계。방법：선취2011년6월-2013년6월재아과치료적만기결직장암환자，공계102례，대기진행UGT1A1*28/*6기인검측，수방기록환자행이립체강화료후적불량반응화근기료효，비교불동기인형환자지간유무차이。결과：불동UGT1A1*28/*6기인형환자중3~4급중성립세포감소화지발성복사발생솔무현저차이。연합UGT1A1*28화*6량위점분석，야생형、단점변이형화쌍점변이형환자중3~4급중성립세포감소발생솔축점승고，삼자유현저차이차승고추세유통계학의의（4.3%、17.4%、57.1%，P=0.005，추세검험P =0.002）。UGT1A1*28기인형대치료유효솔（RR）화질병공제솔（DCR）무현저영향，단UGT1A1*6기인돌변자교야생형자RR、DCR균명현강저（P=0.023，P=0.032）。연합량위점분석，야생형、단점변이형화쌍점변이형환자RR、DCR균유현저차이（P=0.002，P=0.008），차DCR강저추세유통계학의의（95.7%、73.9%、42.9%，추세검험P=0.001）。결론：재예측이립체강독성급료효시，연합검측UGT1A1*28/*6량위점기인교단독검측일개위점경유개치。
Objective:To evaluate the correlations between UGT1A1*28/*6 gene polymorphisms and irinotecan-associated toxicity and efficacy in treatment of advanced colorectal cancer. Methods: The UGT1A1*28/*6 genotypes of 102 advanced colorectal cancer patients treated in our department from June 2011 to June 2013 were detected. The toxicity and efficacy were observed and recorded after irinotecan-based chemotherapy. The difference of toxicity and efifcacy among patients with different genetic polymorphisms were assessed. Results:There was no signiifcant difference in the incidence of Grade 3-4 neutropenia and delayed-onset diarrhea among the patients with different UGT1A1*28 and UGT1A1*6 genotypes. When UGT1A1*28/*6 genotypes were analyzed simultaneously, the patients with double allele mutations had signiifcantly higher incidence of Grade 3-4 neutropenia than those with single allele mutation or wild type (57.1%, 17.4%, 4.3%, respectively;Fisher's exact test P=0.005;Cochran-Armitage trend test P=0.002). UGT1A1*28 genotype had no effect on response rate (RR) and disease control rate (DCR), while the patients with UGT1A1*6 mutation showed worse efficacy (RR and DCR) than those with wild genotype (P= 0.023, P= 0.032). When conjoint analysis of the effect of UGT1A1*28/*6, the differences of RR and DCR were signiifcant in patients with wild type, single and double allele mutation (Fisher's exact test P=0.002,P=0.008), and DCR had a decreased trend with the increase of mutant alleles (95.7%, 73.9%, 42.9%, respectively;Cochran-Armitage trend test P=0.001). Conclusion:Joint detection of UGT1A1*28 and UGT1A1*6 genotype is of more value in prediction of irinotecan-related toxicity and efifcacy than single allele detection.
