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汉族晚期大肠癌ERCC1和XRCC1基因多态性与奥沙利铂化疗敏感相关性的研究 被引量:5

Genetic polymorphism of ERCC1 and XRCC1 correlated with response to oxaliplatin based chemotherapy in advanced colorectal cancer
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摘要 目的:探讨ERCC1Asn118Asn和XRCC1Arg399Gln多态性与中国汉族晚期大肠癌患者对奥沙利铂(Oxaliplatin,L-OHP)一线化疗临床效果的关系。方法:62例晚期大肠癌患者化疗前抽取静脉血并提取DNA,以RT-PCR法对ERCC1、XRCC1基因进行SNP分型。患者接受奥沙利铂为主的化疗方案化疗,比较不同基因型与化疗效果的关系。结果:ERCC1Asn118Asn基因突变频率为:C/C53.23%(33/62),C/T37.10%(23/62),T/T9.67%(6/62);XRCC1Arg399Gln基因突变频率为:G/G50.00%(31/62),G/A37.10%(23/62),A/A12.90%(8/62)。62例患者化疗2~3个周期后评价临床获益率为54.84%。ER-CC1基因Asn118Asn基因型C/C与C/T+T/T在化疗获益组和化疗不敏感组中分布差异有统计学意义,χ2=6.289,P=0.021。XRCC1基因Arg399Gln基因型G/G与G/A+A/A在化疗获益组和化疗不敏感组中分布差异也有统计学意义,χ2=6.513,P=0.021。两者联合多态性分析发现,同时携带ERCC1C/C和XRCC1G/G基因型患者化疗敏感性是同时携带ERCC1C/T+T/T和XRCC1G/A+A/A基因型患者的11.333倍,P=0.002。结论:ERCC1Asn118Asn、XRCC1Arg399Gln基因多态性与中国汉族晚期大肠癌患者接受奥沙利铂一线化疗后的临床效果有关。 OBJECTIVE: To assess whether the polymorphism of ERCC1 Asn118Asn and XRCC1 Arg399Gln has an effect on the clinical outcome in Chinese patients treated with oxaliplatin as first line chemotherapy regimens for advanced coloreetal canc er. METHODS: DNA was extracted from peripheral venous blood before chemotherapy in 62 advanced colorectal cancer patients. Real time PCR was used for genotyping the SNP of ERCC1 and XRCC1. The patients were routinely treated with oxaliplatinbased chemotherapy. The relationship between objective tumor response(OR) and genotypes was studied. RESULTS: ERCC1 Asnl18Asn had three allelotypes in this group and their frequen cies were C/C 53.23%o (33/62), C/T 37.10% (23/62), T/T 9.67% ( 6/62 ) respectively. The fregnoncies of XRCC1 Arg399Gln were G/G 50. 00~ (31/62), G/A 37.10% (23/62), A/A 12.90%(8/62) respectively. The clinical benifit rate for 62 stage Ⅳ cases was 54.84%, including 0 CR,18 PR,16 SD, 28 PD calculated after 2 or 3 cycles. The patients with C/C genotype showed distinctly preponderance compared to those with C/T+ T/T, and there was a statistically difference between the clinical benifit group (CR+PR+SD) and un response group PD, χ^2 =6. 289, P= 0.021, and so was XRCC1 Arg399Gln G/G and G/A--A/A, χ^2=6. 513, P=0. 021. In addition,these two polymorphisms seemed to have synergic effect, with OR being 11. 333 (P= 0. 002) for patients carrying the ERCC1 C/C and XRCC1 G/G genotypes compared with those carrying the ERCC1 C/T-L T/T and XRCC1 G/A+A/A genotypes. CONCLUSION: ERCC1 Asn118Asn and XRCC1 Arg399Gln genetic polymorphisms may be associated with clinical outcomes of Chinese patients with advanced colorectal cancer accepted oxaliplatin as first line.
出处 《中华肿瘤防治杂志》 CAS 2008年第17期1329-1332,共4页 Chinese Journal of Cancer Prevention and Treatment
关键词 药物遗传学 ERCC1 XRCC1奥沙利铂 化疗 大肠癌 pharmacogenetics ERCC1 XRCC1 oxaliplatin chemotherapy colorectal cancer
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参考文献16

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