结直肠癌患者UMPS酶基因多态性与氟尿嘧啶化疗敏感性及毒性相关性研究

Study on the Correlation Between Polymorphism of UMPs Gene and Chemotherapy Sensitivity and Toxicity of Fluorouracil in CRC Patients

目的 探讨中国人群尿苷单磷酸合成酶(UMPS)基因多态性与以氟尿嘧啶为基础的结直肠癌(CRC)化疗方案疗效和不良反应的相关性。方法 70例CRC患者接受以氟尿嘧啶为基础的化疗方案,以Sanger测序方法检测UMPS的基因型,采用实体瘤化疗评价标准(RECIST 1.1)评价疗效,采用SAS 9.2版软件进行数据的统计分析。结果 UMPS基因rs1801019位点的SNP分布与性别、年龄、手术、TNM分期、原发病灶部位、转移、组织病理学类型分类以及肿瘤标志物CEA、CA19-9均无明显相关性(P>0.05)。UMPS基因rs1801019位点,野生型和突变型患者骨髓抑制发生率为62.23%,80.00%,野生型患者骨髓抑制发生率低于突变患者,但差异无统计学意义。UMPS基因的rs1801019位点野生型45例,疾病进展率为24.44%,客观缓解率为22.22%,疾病控制率为75.55%;突变型患者20例,疾病进展率30.00%,客观缓解率为30.00%,疾病控制率为70.00%。UMPS基因的rs1801019位点野生型患者疾病控制率高于突变型患者,而疾病进展率低于突变型患者,但差异无统计学意义(P>0.05)。结论 中国人群UMPS基因rs1801019位点多态性与氟尿嘧啶毒副反应发生率无显著相关性。

Objective To investigate the correlation between UMPS gene polymorphism and the efficacy and adverse reactions of fluorouracil-based chemotherapy for colorectal cancer in the Chinese population.Methods A total of 70 patients with pathologically proven colorectal cancer who received fluorouracil-based chemotherapy were examined by the Sanger sequencing to detect the genotype of UMPS.The efficacy was evaluated by using solid tumor chemotherapy evaluation criteria(RECIST 1.1),and statistical analysis was performed using SAS 9.2 software.Results The SNP distribution of rs1801019 locus in the UMPS gene was not significantly correlated with gender,age,surgery,TNM stage,primary lesion site,metastasis,histopathological classification,tumor markers CEA and CA19-9(P>0.05).The incidence of myeloid suppression in wild type and mutant patients was 62.23%and 80.00%,respectively.The incidence of myeloid suppression in patients with wild type was lower than in patients with mutant type,but there was no significant difference.The disease progression rate,the objective response rate,and the disease control rate were 24.44%,22.22%and 75.55%,respectively for the 45 patients with wild type.The disease progression rate,objective response rate and disease control rate were 30.00%,30.00%,and 70.00%,respectively,for the 20 patients with mutant genotype.The disease control rate of wild-type patients at the rs1801019 locus of UMPS gene was higher than that of mutant patients,while the rate of disease progression was lower than that of mutant patients,but the difference were not statistically significant(P>0.05).Conclusion There is no significant difference between the rs1801019 polymorphism of the UMPS gene and the incidence of fluorouracil toxicity in the Chinese population.