CAJ | 학술논문

目的研究MDR1和ABCG2基因单核苷酸多态性(SNP)与结直肠癌患者伊立替康(CPT-11)化疗疗效及不良反应的关系.方法回顾性收集北京大学肿瘤医院消化肿瘤内科1996年1月至2011年12月行以CPT-11为基础化疗药物的晚期结直肠癌患者的完整临床资料及血液样本,提取血液DNA,用直接测序法检测MDR1和ABCG2基因SNP,分析基因多态性与CPT-11疗效和不良反应的相关性.结果 MDR1 2677 G＞T/A及ABCG2 421 C＞A、34 G＞A和376 C＞T的血标本及肿瘤组织检测SNP结果一致率高,分别为94.4％(34/36)、94.6％(35/37)、95.0％ (38/40)和97.2％(35/36).MDR1 2677 G＞T/A中,野生型(G/G)患者较突变型患者临床获益率高,但差异无统计学意义(P＞0.05)；且在二线化疗的患者中,野生型患者无进展生存期(PFS)明显优于突变型患者(P=0.012).未观察到ABCG2 421 C＞A、34 G＞A和376 C＞T多态性与化疗疗效有相关性(均P＞0.05).同时,未观察到MDR1 2677 G＞T/A、ABCG2 421 C＞A、ABCG2 34 G＞A和ABCG2 376 C＞T多态性与患者3度以上粒细胞减少及腹泻相关.结论在晚期结直肠癌患者中,MDR1 2677 G＞T/A可能作为分子标记物来预测伊立替康方案化疗疗效.
목적 연구MDR1화ABCG2기인단핵감산다태성(SNP)여결직장암환자이립체강(CPT-11)화료료효급불량반응적관계.방법 회고성수집북경대학종류의원소화종류내과1996년1월지2011년12월행이CPT-11위기출화료약물적만기결직장암환자적완정림상자료급혈액양본,제취혈액DNA,용직접측서법검측MDR1화ABCG2기인SNP,분석기인다태성여CPT-11료효화불량반응적상관성.결과 MDR1 2677 G＞T/A급ABCG2 421 C＞A、34 G＞A화376 C＞T적혈표본급종류조직검측SNP결과일치솔고,분별위94.4％(34/36)、94.6％(35/37)、95.0％ (38/40)화97.2％(35/36).MDR1 2677 G＞T/A중,야생형(G/G)환자교돌변형환자림상획익솔고,단차이무통계학의의(P＞0.05)；차재이선화료적환자중,야생형환자무진전생존기(PFS)명현우우돌변형환자(P=0.012).미관찰도ABCG2 421 C＞A、34 G＞A화376 C＞T다태성여화료료효유상관성(균P＞0.05).동시,미관찰도MDR1 2677 G＞T/A、ABCG2 421 C＞A、ABCG2 34 G＞A화ABCG2 376 C＞T다태성여환자3도이상립세포감소급복사상관.결론 재만기결직장암환자중,MDR1 2677 G＞T/A가능작위분자표기물래예측이립체강방안화료료효.
Objective To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer(CRC).Methods Clinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected,and their blood samples were collected accordingly.Genomic DNA was extracted from blood samples.The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method.The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.Results Allele frequencies of MDR1 2677 G＞T/A,ABCG2 421 C＞A,34 G＞A,376 C＞T were comparable with previous studies.Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent.Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype,while the differences were not significant.The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012).There were no significant correlations between ABCG2 421 C＞A,34 G＞A,376 C＞T and chemotherapy efficacy.No significant correlations were observed between MDR1 2677 G＞T/A,ABCG2 421 C＞A,ABCG2 34 G＞A,ABCG2 376 C＞T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.Conclusion MDR1 2677 G＞T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.