晚期大肠癌患者血清XRCC1基因多态性与奥沙利铂化疗疗效相关性的研究

Genetic polymorphism of XRCC1 correlated with response to oxaliplatin based treatment in advanced colorectal cancer

目的：探讨XRCC1Arg399Gln（G—A）基因多态性与晚期大肠癌对以奥沙利铂为主的化疗敏感性的关系。方法：晚期大肠癌患者99例（Ⅲ期37例，Ⅳ期62例），以奥沙利铂为主的方案化疗，62例Ⅳ期患者2～3个周期后进行临床疗效评价，99例患者统计至疾病进展时间（TTP）。应用TaqMan-MGB探针等位基因分型技术进行基因分型。结果：52．53％为G／G，9．09％为A／A，38．38％为G／A。Ⅳ期62例患者化疗后临床获益率（CR＋PR＋SD）为54．84％，G／G、G／A＋A／A在化疗敏感组与不敏感组中的分布具有统计学意义（χ^2=6．513，P=0．021；OR=3．870，95％CI=1．341～11．172，P=0．012）。99例患者中位TTP7个月，G／G基因型10个月，G／A＋A／A基因型5个月，两者比较差异有统计学意义，χ^2=29．20，P〈0．01。结论：XRCC1 Arg399Gln基因多态性可能与晚期大肠癌患者对奥沙利铂化疗的敏感性与生存时间相关。

OBJECTIVE： To examine the association between genetic polymorphisms of XRCC1 Arg399Gln （G→A） and response to oxaliplatin-based chemotherapy of advanced colorectal cancer. METHODS： Totally 99 patients （37 in stage Ⅲ , 62 in stage IV） with advanced colorectal cancer were treated with oxaliplatin-based chemotherapy,and clinical response of 62 patients in stage IV were evaluated after 2 to 3 cycles; all patients （99） were evaluated time to progress （TTP）. XRCC1 genotypes were detected by TaqManMGB probe methods. RESULTS： 52.53% were G/G genotype, 9.09% were G/A genotype, and 38.38% were G/A genotype. The clinical benefit rate （CR＋PR＋SD） was 54.84%. Patients with G/G genotype showed distinctly preponderance compared to those with G/A＋ A/A, between response group and un-response group （χ^2=6.513, P=0.021; OR=3.870, 95 % CI=1. 341--11.172 , P=0. 012）. The median TTP of all patients was 7 months; G/G genotype was 10 months ; G/A and A/A was 5 months. There was a significant difference between them, χ^2=29.20, P〈0.01. CONCLUSION： The results suggest that the XRCC1 Arg399Gln genetic polymorphisms may be associated with clinical responses to oxaliplatin-based chemotherapy and survival time in advanced colorectal cancer,