食管及贲门癌变患者亚甲基四氢叶酸还原酶、胸腺嘧啶合成酶基因多态性分析  

Analasis of methylenetetrahydrofolate reductase and thymidylate synthase gene polymorphisms of esophageal and cardia cancer patients

作　　者：冯常炜[1] 范宗民[1] 高珊珊[1] 何欣[1] 郭花芹[1] 殷丽明 刘宾[3] 张延瑞[4] 王俊宽[1] 刘卫娜[1] 刘小莉[1] 郭涛[1] 王苒[1] 江亚南[1] 孙哲[1] 侯晓华[5] 王立东[1] 

机构地区：[1]郑州大学医学实验中心癌症研究室河南省食管癌重点开放实验室郑州大学第一附属医院内科,郑州450052 [2]安阳市肿瘤医院检验科,安阳455000 [3]首都医科大学同仁医院消化内科,北京100730 [4]河南省人民医院消化内科,郑州450003 [5]华中科技大学同济医学院附属协和医院消化内科,武汉430030

出　　处：《郑州大学学报（医学版）》2006年第1期10-14,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家杰出青年科学基金资助项目30025016;河南省高校创新人才工程基金资助项目1999125;河南省医学科技攻关基金资助项目20058;河南省食管癌重点开放实验室基金资助项目20050227;郑州大学211工程基金资助项目

摘　　要：目的：探讨血清叶酸代谢关键酶亚甲基四氢叶酸还原酶（MTHFR）与胸腺嘧啶合成酶（TS）基因多态性与食管及贲门癌易感性的关系。方法：选取安阳地区病理证实的275例食管鳞癌（SCC）及129例贲门腺癌（GCA）患者和315例年龄性别与其匹配的正常对照人群，采用PCR基础上的限制性片段多态检测法（PCR—RFLP）对其NTHFR和TS各基因型进行分析。结果：①对照组MTHFR677CC、CT及TT基因型的分布频率分别为24％、45％和31％；SCC组分别为19％、38％和43％；GCA组分别为19％、35％和46％。对照组TSER3R／3R（4R）、2R／3R及2R／2R基因型的分布频率分别为64％、34％和2％；SCC组分别为62％、35％和4％；在GCA组，分别为63％、30％以及7％。②与MTHFR677CC及MTHFR677CT两基因型相比，TT携带者患SCC的危险度升高1．62倍（OR=1．62，95％可信区间（CI）为1．15～2．30，P=0．006），而GCAOR=1．8l（95％CI为1．17—2．81，P=0．008）。③与其他基因型相比，纯合突变型（TSER2R／2R）患SCC的危险度升高2．44倍（OR=2．44，95％CI为0．89～6．73，P=0．084），患GCA的危险度升高3．94倍（OR=3．94，95％CI为1．29～12．0，P=0．016）。④相对于无基因突变者，仅有MTHFR677TT者患SCC的危险度升高1．60倍（95％CI为1．13—2．28），患GCA的危险度升高1．84倍（95％CI为1．17～2．88），仅有TSER2R／2R者患SCC的危险度升高1．89倍（95％CI为0．62—5．79），差异无统计学意义，但患GCA的危险度升高3．56倍（95％CI为1．03～12．3），双突变型组合（MTHFR677TT和TSER2R／2R）携带者在SCC组中占1．5％，在GCA组中占3．1％，在对照组中未检测到。结论：突变型MTHFR677TT及TSER2R／2R增加安阳地区人群SCC与GCA的易感性，当二者共同存在时，肿瘤的易感性更高。MTHFR与TS基因多态的存在可能是SCC与GCA地理分布一致性的遗传学基础之一。Aim： To evaluate the relationship between the polymorphisms of methylenetetrahydrofolate reductase （MTHFR） and thymidylate synthase （TS） gene and the high susceptibility risk of esophageal squamous cell cancer （SCC） and gastric cardia adenocarcinoma （GCA）. Methods： A total of 275 cases of SCC and 129 cases of GCA, which were histopathologically confirmed,and with matched age and sex frequencies were subjected to analyze genotypes of MTHFR and TS gene by PCR-RFLP technique. Results： The frequencies of MTHFR677 genotypes CC, CT, and TT were 24% ,45% and 31% in controls, respectively; and 19% , 38% and 43% in patients with SCC, respectively; and 19% , 35% and 46% in those with GCA, respectively. For TSER,the frequencies of the TSER 3R/3R or 3R/4R, 2R/3R, and 2R/2R were 64% ,34% and 2% , respectively, in controls; 62% , 35% and 4% , respectively, in patients with SCC; and 63% , 30% and 7% , respectively, in patients with GCA. The sex-and age-adjusted OR for the MTHFR677 TT genotype indicated a 1.62- （95% CI 1.15 -2.30; P〈0.05） and 1.81-（95% CI 1.17-2.81;P〈0.05） fold increased risk for developing SCC and GCA, respectively, when compared with the CC/CT genotype. The adjusted OR for the TSER 2R/2R genotype showed a2.44- （95% CI0.89 -6.73;P〉0.05） and 3.94-（95% CI1.29-12.0;P〈0.05） fold increased risk for developing SCC and GCA, respectively, when compared with the other TSER genotypes. Using subjects with the combination of MTHFR677 CC/CT and the TSER 2R/3R or 3R/3R genotypes as the reference group, increased risk for developing SCC was observed in individuals with combination of the MTHFR677 TT and TSER genotypes other than 2R/2R （ adjusted OR = 1.60,95% CI 1.13- 2.28 ） , and in individuals with combination of the MTHFR677 CC/CT and the TSER 2R/2R （ adjusted OR = 1.89, 95% CI 0. 62 - 5.79 ） ; similarly, increased risk for developing GCA was also found in individuals with combination of the MTHFR677 TT and the TSER 2R/3R or 3R/3R （adjusted OR = 1.84, 95% CI 1.17 -2.8

关 键 词：食管肿瘤 鳞癌 贲门肿瘤 腺癌 基因多态 遗传易感性 亚甲基四氢叶酸还原酶 胸腺嘧啶合成酶 

分 类 号：R735.1[医药卫生—肿瘤]