胃癌病人ERCC1和XPD基因多态性与奥沙利铂化疗预后关系

目的了解DNA损伤修复基因ERCC1 Asn118Asn和XPD Lys751Gln多态性与接受以奥沙利铂为基础化疗的晚期胃癌病人预后的关系。方法 90例晚期胃癌病人接受奥沙利铂化疗前抽取静脉血并提取DNA,应用real-ti me PCR法进行基因分型。比较病人不同基因型与生存期的关系。结果晚期胃癌病人ERCC1Asn118Asn基因型频率为C/C 47.78%,C/T42.22%,T/T10.00%;XPD基因型频率分别为A/A80.00%,A/C16.67%,C/C 3.33%。90例胃癌病人中位无疾病进展生存期（TTP）6.4个月,总生存期（OS）9.5个月。ERCC1C/C基因型病人中位TTP为6.6个月,OS为9.7个月;C/T＋T/T型病人中位TTP为6.1个月,OS为9.1个月,二者差异无统计学意义（P〉0.05）。XPD A/A基因型病人中位TTP为6.7个月,OS为9.7个月;A/C＋C/C基因型病人中位TTP为4.8个月,OS为7.8个月,二者差异有统计学意义（χ2=20.244、17.113,P〈0.05）。同时携带ERCC1 C/C及XPD A/A基因型、ERCC1 C/C及XPD A/C＋C/C基因型、ERCC1 C/T＋T/T及XPD A/A基因型、ERCC1 C/T＋T/T及XPD A/C＋C/C基因型的病人中位TTP分别为6.9、4.7、6.3和5.0个月,OS为9.9、7.7、9.3、8.0个月,4组差异有统计学意义（χ2=18.331、12.742,P〈0.05）。结论 XPD Lys751Gln基因多态性与以接受奥沙利铂为基础化疗的晚期胃癌病人的生存期有关,ERCC1 Asn118Asn基因多态性与接受奥沙利铂为基础化疗的晚期胃癌病人的生存期无关。

THE RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF ERCC1,XPD AND PROGNOSIS OF GASTRIC CANCER PATIENTS TREATED WITH OXALIPLATIN-BASED CHEMOTHERAPY

Objective To study the relationship between the polymorphism of excision repair cross complementation group 1（ERCC1） Asn118Asn,XPD Lys751Gln and the prognosis of advanced gastric cancer patients treated with oxaliplatin-based chemotherapy. Methods DNA was extracted from venous blood of 90 patients before chemotherapy.Genotyping was done with real-time PCR.The relationship between different genotypes and survival time was analyzed. Results The mutation rates of ERCC1 Asn118Asn in the patients were C/C 47.78%,C/T 42.22% and T/T 10.00%;that of XPD Lys751Gln were A/A 80%,A/C 16.67% and C/C 3.33%.Of the 90 patients,the median survival time without progression of the disease（MSTWPD） was6.4 months and the overall survival time（OST） was 9.5 months.The MSTWPD in patients with ERCC1 CC genotype was 6.6 and OST was 9.7 months,respectively;in those with C/T＋T/T,the MSTWPD and OST were 6.1 and 9.1 months,respectively,the differences were not significant between the two groups（P0.05）.In the patients with XPD A/A genotype,the MSTWPD and OST were 6.7 and 9.7 months;in those with XPD A/C ＋ C/C,MSTWPD and OST were 4.8 and 7.8 months,with a significant difference between them（χ2=20.244,17.113;P0.05）.The MSTWPD of patients with simultaneous ERCC1 C/Cand XPD A/A,ERCC1 C/C and XPD A/C＋C/C,ERCC1 C/T＋T/T and XPD A/A,ERCC1 C/C＋T/T and XPD A/C＋C/C was 6.9,4.7,6.3,and 5.0 months（χ2=18.331,P0.05）,and OST was 9.9,7.7,9.3 and 8.0 months（χ2=12.742,P0.05）,respectively,the differences among the four groups were statistically significant. Conclusion The life span of patients with advanced gastric cancer treated with oxaliplatin-based chemotherapy is associated with genetic polymorphism of XPD Lys751Gln,but is not related to that of ERCC1 Asn118Asn.