山东地区汉族人群中TGFβ1及TGFβR2单核苷酸多态性在大肠癌中的分布特征  

Relationships of TGFβ1 and TGFβR2 gene polymorphisms with colorectal cancer in Chinese Han population in Shandong area

作　　者：邢培祥[1] 王永乐 阚士锋[1] 杨发林[1] 姜金波[2] 司元全[4] 王爱兰[5] Xing Peixiang;Wang Yongle;Kan Shifeng;Yang Falin;Jiang Jinbo;Si Yuanquan;Wang Ailan(Department of Clinical Laboratory,Qilu Hospital,Shandong University,Jinan 250012,China（Xing Pei-xiang,Kan Shifeng,Yaag Falin;Department of Clinical Laboratory,Shandong Changle People＇s Hospital,Weifaag 262400,China（Wang Yongle;Department of General Surgery,Qilu Hospital,Shandong Universi-ty,Jinan 250012,China（Jiang Jinbo;Department of Clinical Laboratory,Shangdong Provincial Hospital,Jinan 250021,China（Si Yuanquan;Department of Clinical Laboratory,Shandong Cancer Hospital and In-stitute,Jinan 250117（Wang Ailan)

机构地区：[1]山东大学齐鲁医院检验科,济南250012 [2]山东大学齐鲁医院检验科普通外科,济南250012 [3]山东省昌乐县人民医院检验科,潍坊262400 [4]山东省立医院检验科,济南250021 [5]山东省肿瘤医院检验科济南,250117

出　　处：《中华微生物学和免疫学杂志》2018年第10期768-773,共6页Chinese Journal of Microbiology and Immunology

基　　金：山东省医药卫生科技发展计划项目（2013WSB20011）

摘　　要：目的探讨转移生长因子-βl（TGFβ1）及转移生长因子β受体-2（TGFβR2）基因多态性与大肠癌发生发展的关系。方法采用基因芯片技术检测TGFβ1-509C／T及＋869T／C单核苷酸多态性（SNP），并采用ELISA测定TGFβ1血清水平；以限制性片段长度多态性聚合酶链反应（PCR-RFLP）检测TGFβR2-875G／A SNP，并以免疫组化检测TGFβR2表达水平。通过病例-对照研究分析490例大肠癌与TGFβ1-509／＋869及TGFβR2-875SNP的关系。采用X^2、t检验行相关指标的比较分析；以比值比（OR）及其95％置信区间（95％CI）评估相对风险。结果（1）大肠癌组TGFβR2-875GG及G频率均显著高于对照组（X^2GG=4．65，P=0．031；X^2G=4．95，P=0．026），TGFβ1-509／＋869SNP各基因型及等位基因频率与对照组比较差异均无统计学意义（P〉0．05）。（2）直肠癌、管状腺癌及高化管状腺癌TGFβR2-875GG及G频率均显著高于对照组，其OR（95％CI）分别为：1．39（1．02～1．95）、1．51（1．14-2．00）、1．68（1．19～2．38）及1．32（1．01～1．73）、1．45（1．14～1．85）、1．62（1．18～2．21）。（3）大肠癌组TGFβR2-875G携带者TGFβ1血清水平显著高于相应AA携带者（t=-3．42，P〈0．05）及对照组AA携带者（t=-5．09，P〈0．001）。（4）直肠癌TGFβR2-875G表达显著下调．低于相应AA携带者（P=0．047）及对照组（P=0．027）。结论TGFβR2-875SNP与大肠癌相关，TGFβR2-875GG可能是大肠癌易感风险因素。Objective To study the relationships of TGFI31 （-509C/T, ＋869T/C） and TGFβR2 （-875 G/A） single nucleotide polymorphisms （SNPs） with colorectal cancer （CRC） in Chinese Han popu-lation in Shandong. Methods TGFβ1-509C/T and ＋869T/C SNPs in a total of 490 patients with CRC were detected using gene chip. TGFβR2-875 SNPs was analyzed using PCR-RFLP. TGFβ1 concentrations in serum samples were measured by ELISA. Immunohistochemistry was used to detect the expression of TGFβR2. The relationships of TGFβ1 （-509C/T, ＋869T/C） and TGFβR2 （-875 G/A） SNPs with CRC were analyzed through a case-control study. Chi-square test or t test was used for statistical analysis. Rela-tive risk was estimated by odds ratio （OR） and 95% confidence interval （95% CI）. Results No signifi-cant difference in genotype or allele frequency at TGFβ1 -509/＋869 was found between patients with CRC and healthy subjects （P〉0.05）. The frequencies of TGFI3R2 -875GG genotype and -875G allele in pa- tients with CRC were significantly higher than those in healthy subjects （ -875GG： X^2 = 4.65, P = 0. 031, OR = 1.32, 95% CI = 1.03-1.71 ; -875G： X^2 = 4.95, P = 0. 026, OR = 1.29, 95% CI = 1.03-1.61 ）. Com- pare with the healthy control group, higher frequencies of TGFβR2 -875GG genotype and -875G allele were also detected in rectal cancer （ -875GG： P = 0.04, OR = 1.39, 95% CI = 1.02-1.95 and -875G： P = 0. 045, OR = 1.32, 95% CI = 1.01-1.73 ）, tubular adenocarcinoma （ -875GG： P = 0. 004, OR = 1.51, 95 % CI = 1.14-2.00 and -875 G ： P = 0. 003, OR = 1.45, 95 % CI = 1.14-1.85 ） and highly differentiated tu- bular adenoearcinoma （ -875GG： P=0.003, OR= 1.68, 95% CI= 1.19-2.38 and -875G： P=0. 002, OR = 1.62, 95% CI = 1.18-2.21 ） groups. The serum TGFβ1 levels in TGFβR2 -875G carriers with CRC were significantly higher than those in TGFβR2 -875AA carriers in both CRC （ t = -3.42, P〈0.05 ） and healthy control （ t = -5.09, P〈0. 001 ） groups. TGFβR2 expression in -875G car

关 键 词：大肠癌 TGFβR2 多态性 单核苷酸 

分 类 号：R735.34[医药卫生—肿瘤]