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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 plays an important role in tumorigenesis by controlling cell proliferation and differentiation. The plasma level of TGFβ1 and the expression of its receptor Ⅱ are associated with tumorigenesis closely related. This study was designed to investigate the relationship between TGFβ1 gene TGFB1 C-509T, TGFB1 Leu10Pro, TGFBR2 G-875A single nucleotide polymorphisms and genetic susceptibility to gastric cancer in Chinese Han population in Yixing, East China. Methods: This study is a case-control study. Totally 256 patients with histologically confirmed gastric adenocarcinoma in Yixing high incidence area of gastric cancer and 303 healthy control subjects with matched age and sex frequency were enrolled in this study. Primer mismatch restriction analysis (PCR-PCR) TGFB1 C-509T, TGFB1 Leu10Pro and TGFBR2 G-875A polymorphisms were tested by multivariate logistic analysis to calculate the odds ratio (OR) and its 95% confidence interval (CI) And the risk of gastric cancer. RESULTS: The polymorphisms of TGFB1 C-509T and TGFB1 Leu10Pro were highly linkage disequilibrium (De = 0.86). Compared with individuals carrying the wild homozygous genotypes (-509CC and 10Leu / Leu), the genotypes carrying mutations (-509CT / TT (OR = 0.51, 95% CI = 0.36 to 0.74) and 34% (adjusted OR = 0.66, 95% CI = 0.45 to 0.98, respectively) for individuals with and without 10Leu / Pro or Pro / . There was a significant dose-response relationship between the number of mutations in TGFB1 C-509T and TGFBR2 G-875A loci and the risk of gastric cancer (x2 = 15.70, P <0.001). With the increase of the number of mutated sites , The risk of suffering from gastric cancer decreased significantly. Further stratification analysis showed that this protective effect was significantly associated with age-dependents ≤60 years (adjusted OR = 0.42,95% CI = 0.23-0.79) and non-drinkers (corrected OR = 0.45,95% CI = 0.27-0.74) More obvious. Conclusion: The polymorphisms of TGFB1 and TGFBR2 may be related to the genetic susceptibility to gastric cancer in Han population in Yixing, eastern China.