摘要
目的探讨DNA甲基转移酶3b(DNMT3b)基因单核苷酸多态性(SNPs)与晚期结直肠癌患者应用FOLFOX4方案化疗疗效的关系。方法采用SNP预测软件筛选HapMap数据库中国汉族人群DNMT3b基因的4个标签SNPs(rs6119954、rs4911107、rs4911259、rs8118663)及启动子区2个SNPs(rs1569686、rs2424913),采用直接测序法检测178例晚期结直肠癌患者外周血DNA中以上SNPs位点的基因分布情况;采用RECIST 1.1标准评价以上患者接受FOLFOX方案化疗4个周期的近期疗效,并将患者分为有效组(CR+PR)和无效组(SD+PD),分析不同化疗效果与临床病理参数(年龄、性别、部位、肿瘤大小、病理类型和分化程度)及以上SNPs位点基因型、等位基因的关系。结果 178例晚期结直肠癌患者DNMT3b rs6119954、rs1569686、rs4911107、rs4911259、rs8118663和rs2424913基因多态性位点各基因型分布与预测值的差异均无统计学意义(P>0.05),符合Hardy-Weinberg平衡。178例晚期结直肠癌患者经4个周期化疗后,获CR 4例、PR 45例、SD 88例、PD41例,故分为有效49例和无效129例。FOLFOX4化疗效果与年龄、性别、部位、肿瘤大小及病理类型均无关,而与分化程度有关(P<0.05)。rs6119954及rs2424913中携带突变等位基因者的化疗有效率较低,且化疗无效的风险升高,以上差异均有统计学意义(P<0.05);其余SNPs位点基因分布与疗效及无效风险均无关(P>0.05)。结论 DNMT3b rs6119954及rs2424913与晚期结直肠癌患者FOLFOX4方案的疗效有关,且携带rs6119954 A或rs2424913 T等位基因者化疗无效的风险较高,对于预测晚期结直肠癌患者FOLFOX4方案的效果可能具有一定价值。
Objective To investigate the relationship between the single nucleotide polymorphisms（ SNPs） of DNA methyl transferase 3b（ DNMT3b） gene and the efficacy of FOLFOX4 regimen in patients with advanced colorectal cancer. Methods The SNP predictive software was used to screen 4 target SNPs（ rs6119954,rs4911107,rs4911259,rs8118663） and 2 SNPs（ rs1569686,rs2424913） in the promoter region in the Hap Map database of DNMT3 b gene in Chinese Han population. The distribution of SNPs in peripheral blood DNA of 178 patients with advanced colorectal cancer were detected by direct sequencing. RECIST 1. 1 standard was used to evaluate the short term efficacy of patients receiving FOLFOX regimen after 4 cycles of chemotherapy. The patients were divided into effective group（ CR＋PR） and ineffective group（ SD＋PD）. We analyzed different chemotherapy effects and clinical pathological parameters（ age,sex,location,tumor size,pathological type,clinical stage and differentiation degree） as well as the relationship between the SNPs locus genotype and allele. Results There was no significant difference between genotype distribution and predictive value of DNMT3 b rs6119954,rs1569686,rs4911107,rs4911259,rs8118663 and rs2424913 in 178 patients with advanced colorectal cancer（ P〉0. 05）. After 4 cycles of chemotherapy,there were 4 cases of CR,45 cases of PR,88 cases of SD and 41 cases of PD and then the patients were divided into effective group（ n = 49） and ineffective group（ n = 129）. The effect of FOLFOX4 chemotherapy was not related to age,sex,location,tumor size and pathological type,but was related to degree of differentiation（ P〈0. 05）. In rs6119954 and rs2424913,the effective rate of chemotherapy was low,and the risk of ineffective chemotherapy was increased with statistical significance difference（ P〈0. 05）. The distribution of the remaining SNPs loci was not related to the efficacy and the risk of invalid efficacy（ P〈0. 05）. Conclusion DNMT3 b rs6119954 and rs2424913 were
出处
《临床肿瘤学杂志》
CAS
2016年第6期519-524,共6页
Chinese Clinical Oncology
