Lynch综合征相关结直肠癌患者TYMS基因多态性研究

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摘要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。

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	聂辰1 高磊2 王俊懿3 李月廷1

关键词 ： Lynch综合征, 结直肠癌, 胸苷酸合成酶, 氟尿嘧啶

Abstract：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.

Key words： Lynch syndrome Colorectal cancer Thymidylate synthase Fluorouracil

基金资助:北京市海淀区支持核心区自主创新和产业发展专项资金项目（S201319）。

通讯作者: 李月廷（1964.8-），男，主任医师，硕士生导师；研究方向：结直肠癌的遗传、诊断和治疗。王俊懿（1979.5-），女，工程师；研究方向：现代生物技术实验室的应用及业务流程管理。

引用本文:

聂辰1 高磊2 王俊懿3 李月廷1. Lynch综合征相关结直肠癌患者TYMS基因多态性研究[J]. 中国医药导报, 2021, 18(11): 100-104.
NIE Chen1 GAO Lei2 WANG Junyi3 LI Yueting1. Polymorphism of TYMS gene of patients with colorectal cancer associated with Lynch syndrome. 中国医药导报, 2021, 18(11): 100-104.

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[1] Lynch HT，Shaw MW，Magnuson CW，et al. Hereditary factors in cancer [J]. Arch Intern Med，1966，117（2）：206-212.
[2] Vasen HFA，Mecklin JP，Khan PM，et al. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer （ICG-HNPCC） [J]. Dis Colon Rectum，1991，34（5）：424-425.
[3] Vasen HFA，Watson P，Mecklin JP，et al. New clinical criteria for hereditary nonpolyposis colorectal cancer （HNPCC，Lynch syndrome） proposed by the International Collaborative Group on HNPCC [J]. Gastroenterology，1999， 116（6）：1453-1456.
[4] Rodriguez-Bigas MA，Boland CR，Hamilton SR，et al. A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome：Meeting highlights and Bethesda guidelines [J]. J Natl Cancer Inst，1997，89（23）：1758-1762.
[5] Umar A，Boland CR，Terdiman JP，et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer （Lynch syndrome） and microsatellite instability [J]. J Natl Cancer Inst，2004，96（4）：261-268.
[6] 中国抗癌协会大肠癌专业委员会遗传学组.遗传性结直肠癌临床诊治和家系管理中国专家共识[J].中华肿瘤杂志，2018，40（1）：64-77.
[7] Giardiello FM，Allen JI，Axilbund JE，et al. Guidelines on genetic evaluation and management of Lynch syndrome：a consensus statement by the US Multi-society Task Force on colorectal cancer [J]. Am J Gastroenterol，2014，109（8）：1159-1179.
[8] Sargent DJ，Marsoni S，Monges G，et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer [J]. J Clin Oncol，2010，28（20）：3219-3226.
[9] Popat S，Hubner R，Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis [J]. J Clin Oncol，2005，23（3）：609-618.
[10] 周岗.56例结直肠癌患者ERCC1/TYMS基因表达和KRAS通路的相关性研究[J].感染、炎症、修复，2017，18（4）：210-213.
[11] Hamzic S，Kummer D，Froehlich TK，et al. Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities：An IPD meta-analysis [J].Pharmacol Res，2020，152（2）：104594.
[12] Friedrichs K，Gluba S，Eidtmann H，et al. Overexpression of p53 and prognosis in breast cancer [J]. Cancer，1993， 72（12）：3641-3647.
[13] Feng RM，Zong YN，Cao SM，et al. Current cancer situation in China：good or bad news from the 2018 Global Cancer Statistics? [J]. Cancer Commun （Lond），2019，39（1）：22.
[14] Monahan KJ，Bradshaw N，Dolwani S，et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology （BSG）/Association of Coloproctology of Great Britain and Ireland （ACPGBI）/United Kingdom Cancer Genetics Group （UKCGG） [J]. Gut，2020，69（3）：411-444.
[15] Lynch HT，Boland CR，Gong G，et al. Phenotypic and genotypic heterogeneity in the Lynch syndrome：Diagnostic，surveillance and management implications [J]. Eur J Hum Genet，2006，14（4）：390-402.
[16] Jin HY，Liu X，Li VK，et al. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer [J]. BMC Cancer，2008，8：44.
[17] 金黑鹰，丁义江，刘秀芳，等.修订Bethseda标准筛选遗传性非息肉病性结直肠癌患者的队列研究[J].中华医学杂志，2007，87（21）：1445-1447.
[18] Schwarzenbach H. Predictive diagnostics in colorectal cancer：impact of genetic polymorphisms on individual outcomes and treatment with fluoropyrimidine-based chemotherapy [J]. EPMA J，2010，1（3）：485-494.
[19] Spears CP，Gustavsson BG，Mitchell MS，et al. Thymidylate synthetase inhibition in malignant tumors and normal liver of patients given intravenous 5-fluorouracil [J]. Cancer Res，1984，44（9）：4144-4150.
[20] 曾令海，王亚旭，谢凯，等.ERCC1、BRCA1、TYMS的mRNA表达水平和UGT1A1多态性检测在结直肠癌患者个体化化疗中的临床意义[J].现代医药卫生，2014，30（12）：1761-1764.
[21] 刘志强，李守淼，张伟，等.分子诊断在结直肠癌术后治疗中的应用[J].肿瘤基础与临床，2017，30（5）：417-421.
[22] Gibson TB. Polymorphisms in the thymidylate synthase gene predict response to 5-fluorouracil therapy in colorectal cancer [J]. Clin Colorectal Cancer，2006，5（5）：321-323.
[23] Yu KH，Wang WX，Ding YM，et al. Polymorphism of thym-idylate synthase gene associated with its protein expression in human colon cancer [J]. World J Gastroenterol，2008，14（4）：617-621.
[24] Gusella M，Padrini R. G＞C SNP of thymidylate synthase with respect to colorectal cancer [J]. Pharmacogenomics，2007，8（8）：985-996.
[25] Onwe EE，Ghani FA，Abdullah M，et al. Predictive Potential of PD-L1，TYMS，and DCC Expressions in Treatment Outcome of Colorectal Carcinoma [J]. Adv Exp Med Biol，2020，97-112.
[26] 胡德升，高磊，王江，等.外周血胸苷酸合成酶基因表达与中晚期结直肠癌患者FOLFOX4化学治疗敏感性和预后的相关性[J].新乡医学院学报，2020，37（10）：930-934.