消化道肿瘤患者MTHFR基因多态性与5-氟尿嘧啶化疗不良反应的相关性研究  

Relationship between MTHFR Gene Polymorphisms and Adverse Events by 5-FU in Gastrointestinal Cancer

作　　者：周琰 王蓓丽 张春燕 潘柏申 郭玮 ZHOU Yan;WANG Bei-li;ZHANG Chun-yan;PAN Bai-shen;GUO Wei(Department of Laboratory Medicine,Zhongshan Hospital of Fudan University,Shanghai 200032,China;…2.Department of Laboratory Medicine,Xiamen Branch,Zhongshan Hospital of Fudan University,Fujian Xiamen.361015,China)

机构地区：[1]复旦大学附属中山医院检验科,上海200032 [2]复旦大学附属中山医院厦门医院检验科,福建厦门361015

出　　处：《现代检验医学杂志》2020年第3期1-5,38,共6页Journal of Modern Laboratory Medicine

基　　金：上海青年临床医技人才(临床检验专业)培养资助计划(沪医卫基[2016]05号);国家自然科学基金面上项目(81572064,81772263);中山医院管理院内基金(2019ZSGL09);2017年上海市“上海青年临床医技人才(临床检验专业)”培养资助计划;国家自然科学基金青年基金(81902139);上海市临床重点专科建设项目(医学检验科)。

摘　　要：目的在消化道肿瘤患者中,探讨MTHFR 1298A>C和MTHFR 677C>T基因多态性与5-氟尿嘧啶(5-FU)化疗出现不良反应的关系。方法2016年2~6月,入组复旦大学附属中山医院肿瘤内科收治的123例消化道肿瘤患者。提取外周血中的基因组DNA,通过Sanger测序检测MTHFR 1298A>C和MTHFR 677C>T的基因型。随访其中98例含5-FU治疗方案的患者,分析了不同基因型的患者发生毒副反应的类型及严重程度的区别。结果123例消化道肿瘤患者中,MTHFR 1298A>C野生型76例(61.79%),杂合型AC 40例(32.52%),纯合型CC 7例(5.69%)。MTHFR677C>T野生型CC 50例(40.65%),杂合型CT 61例(49.59%),纯合型TT 12例(9.76%)。98例化疗方案中含5-FU的患者中,MTHFR 677C>T突变型(CT和TT)显著增加化疗后发生不良反应的风险(χ^2=4.188,P<0.05);MTHFR 1298A>C突变型(AC和AA)、性别、年龄、治疗方案与使用5-FU产生的相关毒副作用无显著关联性。结论在接受5-FU治疗的消化道肿瘤患者中,MTHFR 677C>T多态性显著增加化疗相关毒副反应的发生风险,该基因可能成为预测氟尿嘧啶类化疗药物发生临床不良事件的风险因素,能够为临床选择合适的治疗方案提供更多的信息。Objective To investigate the relationship of MTHFR 677C>T and MTHFR 1298A>C gene polymorphisms in 5-fluorouracil(5-FU)-based chemotherapy in gastrointestinal cancer.Methods From February 2016 to June 2016,123 gastrointestinal cancer patients were admitted to Zhongshan Hospital of Fudan University.Genomic DNA in peripheral blood was extracted,and MTHFR 1298A>C,MTHFR677C>T gene polymorphisms were detected by Sanger sequencing.A total of 98 patients treated with 5-FU were chosen to observe the adverse events during chemotherapy,and the differences between the adverse event and grades in patients with different genotypes was analyzed.Results Of the 123 patients,MTHFR 1298A>C wild type AA was 76(61.79%),heterozygous AC was 40(32.52%)and homozygous CC was 7(5.69%).MTHFR 677C>T wild type CC was 50 cases(40.65%),heterozygous type CT was 61 cases(49.59%)and homozygous type TT 12 was cases(9.76%).In the 98 gastrointestinal Cancer cases,the incidence of total the incidence of adverse events in the patients carrying the MTHFR 677C>T(CT+TT)genotype was higher than in the WT genotype(CC)(P<0.05).The MTHFR 1298A>C genotype,sex,age and chemotherapy strategy were not associated with the adverse events inducing by 5-FU.Conclusion The MTHFR 677C>T polymorphism significantly increases the risk of chemotherapy-related adverse reactions in gastrointestinal cancer patients treated with 5-FU.The applying of MTHFR polymorphism may be used as a risk factor for predicting clinical adverse events in fluorouracil-based chemotherapy and assist the individualized treatment in gastrointestinal cancer.

关 键 词：5-氟尿嘧啶 亚甲基四氢叶酸还原酶(MTHFR) 基因多态性 不良反应 

分 类 号：R735[医药卫生—肿瘤] R730.43[医药卫生—临床医学]