摘要
目的:探讨DNA损伤修复基因ERCC1 Asn118Asn和XRCC1 Arg399Gln多态性与接受奥沙利铂一线化疗的中国晚期大肠癌患者生存期的关系。方法:99例晚期大肠癌患者化疗前抽取静脉血并提取DNA,以real-time 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,比较不同基因型与患者生存期的关系。结果:ERCC1 Asn118Asn基因位点在所研究的中国大肠癌患者中的突变频率为:C/C50.51%、C/T41.41%、T/T8.08%;XRCC1 Arg399Gln基因突变频率为:G/G52.53%、G/A38.38%、A/A9.09%。99例晚期大肠癌患者中位TTP为7个月。ERCC1C/C基因型患者中位TTP10个月,C/T+T/T型患者中位TTP5个月,二者有显著统计学差异(P<0.01);XRCC1G/G基因型中位TTP10个月,G/A+A/A基因型中位TTP5个月,二者比较差异有显著性(P<0.01)。两个基因联合多态性分析发现,同时携带ERCC1C/C和XRCC1G/G基因型、ERCC1C/C和XRCC1G/A+A/A基因型、ERCC1C/T+T/T和XRCC1G/G基因型、以及ERCC1C/T+T/T和XRCC1G/A+A/A基因型的患者中位TTP分别为11个月、6个月、5个月和5个月,4组比较差异有显著性(P<0.01)。结论:ERCC1 Asn118Asn、XRCC1 Arg399Gln基因多态性与中国晚期大肠癌患者接受奥沙利铂一线化疗后的生存期有关。
Objective: To evaluate the effect of the polymorphisms of excision repair cross complementation group 1 (ERCC1) and X-ray repair cross complementing 1(XRCC1) on the overall survival of advanced colorectal cancer patients who received oxaliplatin-based chemotherapy. Methods: DNA was extracted from peripheral venous blood of 99 advanced colorectal cancer patients before chemotherapy. Real-time PCR was used to type the SNP of ERCC1 and XRCCI. The patients were routinely treated with oxaliplatin-based chemotherapy. The relationship between time to progress (TTP) and genotypes was explored. Results: ERCC1 Asnl18Asn had three allelotypes including C/C, C/T, and T/T, with frequencies of 50.51%, 41.41%, and 8.08%, respectively. XRCC1 Arg399GIn had three allelotypes including G/G, G/A and A/A, with frequencies of 52.53%, 38.38%, and 9.09%, respectively. The mTTP of these 99 patients was 7 months. The mTTP was 10 month for patients with C/C genotypes of ERCC1 gene and 5 months for patients with C/T and T/T genotypes of ERCC1 gene, with a significant difference (P〈0.01). The mTTP was 10 months for patients with G/G genotypes of XRCC1 gene and 5 months for patients with G/A and A/A genotypes of XRCC1 gene, with a significant difference (P〈 0.01). These two polymorphisms seemed to have a synergic effect. The mTTP of patients with ERCC1 C/C and XRCC1 G/G, ERCC1 C/C and XRCC1 G/A+A/A, ERCC1 C/T+T/T and XRCC1 G/G, ERCC1 C/C+T/T and XRCC1 G/A+A/A was 11 months, 6 months, 5 months and 5 months, respectively, with a significant difference (P〈0.01). Conclusion: ERCC1 Asn118Asn and XRCC1 Arg399GIn genetic polymorphisms may be associated with TTP of advanced colorectal cancer patients treated with oxaliplatin as the first-line chemotherapy.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2008年第18期1068-1072,共5页
Chinese Journal of Clinical Oncology