Lynch综合征相关结直肠癌患者TYMS基因多态性研究

Polymorphism of TYMS gene of patients with colorectal cancer associated with Lynch syndrome

目的研究北京地区多中心Lynch综合征相关结直肠癌患者胸苷酸合成酶(TYMS)基因多态性,并通过文献分析TYMS基因多态性与该患者群体使用5-氟尿嘧啶化疗效果的关系。方法102例结直肠癌组织均收集自2015年4月—2016年12月于北京市4所医院接受手术治疗的患者,其中男性61例,女性41例。使用免疫组织化学及基因序列检测的方法筛选出Lynch综合征患者,再采用基因测序明确这些患者TYMS基因的多态性。结果在10例Lynch综合征患者中,其中TYMS基因多态性表现为2R/2R和3RC/3RC共4例,表现为2R/3RG、3RC/3RG和3RG/3RG共6例。高表达人群中,男4例、女2例;低表达人群中,男1例、女3例。结论北京地区多中心Lynch综合征结直肠癌患者TYMS基因多态性多数表现为2R/3RG、3RC/3RG或3RG/3RG,与该基因高度表达相关,氟尿嘧啶类药物疗效不佳。但有患者TYMS基因多态性表现为2R/2R或3RC/3RC,与该基因低度表达相关,应用以氟尿嘧啶类药物为基础的化疗方案可收到良好的效果。

Objective To study the polymorphism of thymidylate synthase(TYMS)gene in patients with colorectal cancer associated with Lynch syndrome in Beijing area,and to analyze the relationship between TYMS gene polymorphism and the effect of 5-Fluorouracil chemotherapy by literature.Methods A total of 102 cases of colorectal cancer tissues were collected from patients who underwent surgery in four hospitals in Beijing from April 2015 to December 2016,including 61 males and 41 females.Immunohistochemistry and gene sequence detection methods were used to screen out Lynch syndrome patients,and then the polymorphisms of TYMS genes in these patients were identified by gene sequencing.Results Among 102 patients with colorectal cancer,there were 10 patients with Lynch syndrome.Among them,TYMS gene polymorphisms of 2R/2R and 3RC/3RC were four patients,while 2R/3RG,3RC/3RG and 3RG/3RG were six patients.Among the high-expressing group,there were four males and two females;among the low-expressing group,there were one male and three females.Conclusion Most of the TYMS gene polymorphisms in patients with Lynch syndrome and colorectal cancer in Beijing area are 2R/3RG,3RC/3RG or 3RG/3RG,which are related to the high expression of this gene,and the efficacy of Fluorouracil drugs is not good.The TYMS gene polymorphisms in patients with Lynch syndrome and colorectal cancer in Beijing area are 2R/3RG or 3RG/3RG,which are related to the high expression of this gene,and the efficacy of Fluorouracil drugs is not good.