Effect of polymorphisms of the TGF-β1 gene in patients with glioblastoma

Authors and Affiliations:
Joana Vieira de Castro¹,², Céline S. Gonçalves¹,², Sandra Costa¹,², Paulo Linhares³, Rui Vaz³, Ricardo Nabiço⁴, Júlia Amorim⁴, Marta Viana-Pereira¹,², Rui M. Reis^1,2,5, Bruno M. Costa¹,²

¹ Life and Health Sciences Research Institute, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal;

² ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Campus de Gualtar, 4710-057, Braga, Portugal;

³ Department of Neurosurgery, Hospital São João, Alameda Professor Hernâni Monteiro, 4202-451, Porto, Portugal;

⁴ Department of Oncology, Hospital de Braga, Sete Fontes – São Victor, 4710-243, Braga, Portugal;

⁵ Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331 - Doutor Paulo Prata, Barretos, SP, 14780-000, Brazil

Abstract:
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-β1polymorphism 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.

Journal: Tumor Biology

Link: http://link.springer.com/article/10.1007/s13277-015-3343-0