TGFB1和TGFBR2基因多态与胃癌遗传易感性的关系  

Correlations of Polymorphisms of TGFB1 and TGFBR2 Genes to Genetic Susceptibility to Gastric Cancer

作　　者：周炎[1] 靳光付[2] 蒋国军[3] 王洪敏[3] 谈永飞[3] 丁伟良[4] 王莉娜[2] 陈文森[2] 柯巧[2] 沈靖[2] 徐耀初[2] 沈洪兵[2] 

机构地区：[1]宜兴市人民医院肿瘤科,江苏宜兴214200 [2]南京医科大学公共卫生学院流行病与卫生统计学系,江苏南京210029 [3]宜兴市人民医院外科,江苏宜兴214200 [4]宜兴市人民医院检验科,江苏宜兴214200

出　　处：《癌症》2007年第6期581-585,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金项目(No.30571605;No.30671814);江苏省社会发展支持项目(No.BS2004510)~~

摘　　要：背景与目的:转化生长因子β(transforming growth factor β,TGFβ)信号通路通过控制细胞增殖和分化而在肿瘤的发生发展中发挥重要作用,TGFβ1血浆水平及其Ⅱ类受体的表达水平与肿瘤发生密切相关。本研究拟探讨中国华东宜兴地区汉族人群TGFβ1基因TGFB1 C-509T和TGFB1 Leu10Pro及其Ⅱ类受体基因TGFBR2 G-875A单核苷酸多态与胃癌遗传易感性的关系。方法:本研究为病例对照研究。选取宜兴胃癌高发区组织学确诊的胃腺癌患者256例及年龄和性别频数匹配的对照健康体检人群303例,以引物错配限制分析PCR(primer-introduced restriction analysis-PCR,PIRA-PCR)方法进行TGFB1 C-509T、TGFB1 Leu10Pro及TGFBR2 G-875A多态性检测,应用多元Logistic分析方法计算比值比(odds ratio,OR)及其95%可信区间(confidence interval,CI),以评估不同基因型与胃癌发病风险的关系。结果:TGFB1 C-509T和TGFB1 Leu10Pro多态呈高度连锁不平衡(De=0.86),与携带野生纯合基因型(-509CC和10Leu/Leu)个体相比,携带突变基因型(-509CT/TT和10Leu/Pro或Pro/Pro)的个体患胃癌风险分别显著下降49%(校正OR=0.51,95%CI=0.36～0.74)和34%(校正OR=0.66,95%CI=0.45～0.98)。TGFB1 C-509T和TGFBR2 G-875A两位点突变位点个数与胃癌危险性的降低呈显著的剂量-反应关系(x2=15.70,P<0.001),即随着突变位点个数的增加,患胃癌的危险性显著下降。进一步的分层分析显示,这一保护效应在年龄≤60岁者(校正OR=0.42,95% CI=0.23～0.79)和非饮酒者(校正OR=0.45,95%CI=0.27～0.74)中更为明显。结论:TGFB1和TGFBR2基因多态改变可能与中国华东宜兴地区汉族人群胃癌遗传易感性相关。BACKGROUND ＆ OBJECTIVE： Transforming growth factor β （TGFβ） signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. The concentration of TGFβ1 in plasma and the expression of TGFβ receptor II （TGFβR II ） are correlated to the development of certain tumors, including gastric cancer. This study was to explore the correlations of functional genetic variants in TGFB1 and TGFBR2 genes to the genetic susceptibility to gastric cancer. METHODS._ A case-control study was conducted in Yixing City, a high incidence area of gastric cancer. Polymorphisms of TGFB1 C-509T, TGFB1 Leu10Pro,and TGFBR2 G-875A in 256 gastric cancer patients and 303 cancer-free controls, frequency-matched by age and sex, were determined by primer-introduced restriction analysis-polymerase chain reaction （PIRA-PCR）. Crude and adjusted odds ratios （ORs） and 95% confidence intervals （95% CIs） were measured by multivariate Logistic regression analysis to evaluate the correlations of the polymorphisms to the susceptibility to gastric cancer. RESULTS：The TGFB1 C-509T and TGFB1 Leu10Pro were in high linkage disequilibrium （D＇=0.86）. Compared with wildtype homogenous genetypes -509CC and 10 Leu/Leu, variant genetypes -509CT/TT,10 Leu/Pro, and 10 Pro/Pro decreased the risk of gastric cancer by 49% and 34% （adjusted OR=0.51, 95% Ci=0.36-0.74 for -509CT/TT： adjusted OR=0.66, 95% Ci=0.45-0.98 for 10Leu/Pro or 10Pro/Pro）, The risk of gastric cancer was decreased along with the number of variant sites in the TGFB1 C-509T and TGFBR2 G-875A （X^2=15.70,P 〈0.001）. Stratified analysis showed that the protective effects of the genotypes were obvious in the subjects of no more than 60-year old （OR=0.42, 95% Ci=0.23-0.79） and in non-drinkers （OR=0.45, 95% Ci=0.27-0.74）. CONCLUSION： Genetic variants of TGFB1 and TGFBR2 genes may contribute to the risk of developing gastric cancer in an eastern Chinese population in Yixing city.

关 键 词：胃肿瘤 TGFB1 TGFBR2 单核苷酸多态性 遗传易感性 

分 类 号：R735.2[医药卫生—肿瘤]