Vieira de Castro Joana, Gonçalves Céline S, Costa Sandra, Linhares Paulo, Vaz Rui, Nabiço Ricardo, Amorim Júlia, Viana-Pereira Marta, Reis Rui M, Costa Bruno M
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
Tumour Biol. 2015 Aug;36(8):6525-32. doi: 10.1007/s13277-015-3343-0. Epub 2015 Mar 27.
Transforming growth factor beta (TGF-β) plays an important role in carcinogenesis. Two polymorphisms in the TGF-β1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-β1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-β1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-β1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-β1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.
转化生长因子β(TGF-β)在肿瘤发生过程中发挥着重要作用。据报道,TGF-β1基因中的两个多态性位点(-509C/T和869T/C)会影响胃癌和乳腺癌的易感性。869T/C多态性还与乳腺癌患者的总生存期相关。在本研究中,我们调查了这些TGF-β1多态性与胶质瘤风险及预后的相关性。我们进行了一项病例对照研究,纳入了114例胶质瘤患者和138例无癌对照。通过聚合酶链反应随后进行限制性片段长度多态性分析(PCR-RFLP)来评估单核苷酸多态性(SNP)。采用单因素和多因素逻辑回归分析来计算比值比(OR)和95%置信区间(95%CI)。通过对患者年龄和性别进行校正的Cox回归模型评估TGF-β1 -509C/T和869T/C多态性对胶质瘤患者生存期的影响,并以Kaplan-Meier曲线表示。我们的结果表明,TGF-β1基因多态性-509C/T和869T/C与胶质瘤风险无显著相关性。生存分析显示,与携带CC + CT基因型的患者相比,纯合-509TT基因型与胶质母细胞瘤(GBM)患者更长的总生存期相关(OR,2.41;95%CI,1.06 - 5.50;p = 0.036)。此外,与869TT + TC基因型相比,纯合869CC基因型与GBM患者总生存期的增加相关(OR,2.62;95%CI,1.11 - 6.17;p = 0.027)。总之,本研究表明,TGF-β1 -509C/T和869T/C多态性与胶质瘤发生风险无显著相关性,但可能是GBM患者相关的预后生物标志物。