Replication of GWAS identifies RTEL1, CDKN2A/B, and PHLDB1 SNPs as risk factors in Portuguese gliomas patients

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Replication of GWAS identifies RTEL1, CDKN2A/B, and PHLDB1 SNPs as risk factors in Portuguese gliomas patients

Tuesday, 03.12.2019

Authors and Affiliations:

Viana-Pereira M1,2, Moreno DA3, Linhares P4,5, Amorim J6, Nabiço R6, Costa S1,2, Vaz R4,5, Reis RM7,8,9.

1 School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.

2 ICVS/3B's - PT Government Associate Laboratory, Minho, Portugal.

3 Barretos Cancer Hospital, Molecular Oncology Research Center, Barretos, SP, Brazil.

4 Department of Neurosurgery, Hospital S. João, Porto, Portugal.

5 Faculty of Medicine, University of Porto, Porto, Portugal.

6 Department of Oncology, Hospital de Braga, Braga, Portugal.

7 School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal. 

8 ICVS/3B's - PT Government Associate Laboratory, Minho, Portugal.

9 Barretos Cancer Hospital, Molecular Oncology Research Center, Barretos, SP, Brazil.

 

Abstract:

Diffuse gliomas are the most common malignant primary brain tumors and remain incurable. A better knowledge of the tumor etiology is required. Specific single nucleotides polymorphisms (SNPs) rs4977756 (CDKN2A/B), rs6010620 (RTEL1), rs498872 (PHLDB1), rs2736100 (TERT), and rs4295627 (CCDC26) have been associated with glioma susceptibility and are potential risk biomarkers. This study aimed to analyze five SNPs associated with glioma susceptibility, in the Portuguese population. SNPs were genotyped using the Sequenom MassARRAY platform in 127 gliomas and 180 controls. Unconditional logistic regression models were used to calculate odds ratio (OR) and 95% confidence intervals. The false-positive report probability was also assessed. The associations between polymorphisms and survival were evaluated using the log-rank test. It was found that the AG and GG genotypes of the rs4977756 (CDKN2A/B) were associated with an increased risk of gliomas (OR 1.85 and OR 2.38) and glioblastomas (OR 2.77 and OR 3.94). The GA genotype of the rs6010620 (RTEL1) was associated with a decreased risk of glioblastomas (OR 0.45). We also observed that the GA genotype of the rs498872 (PHLDB1) was associated with an increased risk of gliomas (OR 2.92) and glioblastomas (OR 2.39). No significant risk associations were found for the rs2736100 (TERT) and rs4295627 (CCDC26). In addition, the genotype AA of the rs498872 (PHLDB1) was associated with poor overall survival of gliomas patients (AA vs. GA, p = 0.037). The rs6010620 (RTEL1), rs4977756 (CDKN2A/B), and rs498872 (PHLDB1) are associated with glioma risk in the Portuguese population and these data may contribute to understanding gliomas etiology.

 

Journal: Molecular Biology Reports

 

Linkhttps://link.springer.com/article/10.1007%2Fs11033-019-05178-8