MYH基因变异与散发性大肠癌发病风险的初步研究  

Variation Analysis of the MYH Gene Associated with Sporadic Colorectal Cancer

作　　者：杨柳[1] 朱明[2] 陈森清[2] Hong Tao 张元颖[2] 马国建[1] 李金田[2] 张晓梅[2] Haruhiko Sugimura 周建农[1] 

机构地区：[1]江苏省肿瘤医院普通外科,南京210029 [2]江苏省肿瘤防治研究所遗传与分子生物学室,南京210009 [3]日本浜松医科大学第一病理系

出　　处：《癌变．畸变．突变》2009年第6期435-438,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：江苏省卫生厅医学项目(H200846);中日合作课题项目;江苏省"六大人才高峰"项目(2008-H-21)

摘　　要：背景与目的：初步探讨MYH（MutY homologue，MYH）基因的变异与散发性大肠癌发病风险的关系。材料与方法：应用变性高效液相色谱（denaturing high performance liquid chromatography，DHPLC）和测序技术，对140例大肠癌患者及280名正常对照人群的MYH基因16个外显子区域中的7个（外显子1、7、9、11、13、14和16）区域进行变异筛查，用SPSS统计软件进行数据分析。结果：Exon1区域的变异位点为Exonl-316 G〉A、Exonl-292 G〉A和Intronl＋11 C〉T，3者同时出现在所有变异样本中，且病例组变异危险性均为对照组的8．16倍（P=0．04；OR=8．16，95％C／为1．01—203．70）；Exon16区域的变异为nt1678—80delGTF，病例组中直肠癌患者的变异危险性为结肠癌患者的7．18倍（P=0．04；OR=7．18，95％C／为1．102～165）；Exon11区域查出4例Intron10—2A〉G变异；Exon13区域筛查出2例In．on13＋12C〉T变异；Exon14区域筛查出1种错义变异，即Exon14＋74T〉A，P．V463E；Exon7和Exon9区域未筛查出任何变异。结论：MYH变异可能会增加结直肠癌发病风险，应进行监测管理；未筛查到高加索人群中最常见的Exon7区域的变异，提示人种之间变异存在差别。BACKGROUND AND AIM： To investigate the association between the MYH（MutY homologue） genovariation and eolorectal cancer risk. MATERIALS AND METHODS： Denaturing high performance liquid chromatography （DHPLC） and DNA sequencing were used to delineate the variants in 7 of 16 exon-districts in the 140 colorectal cancer patients and 280 controls. All data was analyzed by SPSS software. RESULTS：Four genovariation sites, Exonl-316 G〉 A, Exonl-292 G 〉 A and Intron 1 ＋ 11 C 〉 T, in exon 1 district were detected in all variants of cases and controls simuhaneouly. The variation frequency in cases was significantly higher than that in controls, genovariation risk in cases was 8.16-fold more than controls（P = 0.04; OR = 8.16, 95% CI = 1.01 ～ 203.70） . A missense variation, Exon14 ＋ 74 T 〉 A, p. V463E, was found in exon 14. A deletion variation, nt 1678-80 del GTT, was found in exon 16. In cases, the rectal cancer genovariation frequency was higher than colon cancer, variation risk in the former was 7.18-fold more than the latter （P = 0.04;OR = 7.18,95% CI = 1. 102-165）. CONCLUSION： MYH variation may function as a risk factor for colorectal cancer development. Most patients had rectal cancer. Similar to other Asian races, the MYH variant frequency in Chinese is lower than Caucasian. No variant is found in and around Exon 7 which is one of the most frequently mutated exons in Caucasians. This indicates that the differences of MYH variants may be related to racial differences.

关 键 词：MYH/MutY HOMOLOGUE MAP 变异 散发 结直肠癌 

分 类 号：R246.5[医药卫生—针灸推拿学] R735.3[医药卫生—中医临床基础]