Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2018; 76(06): 393-398
DOI: 10.1590/0004-282X20180051
ARTICLE

Genetic variants related to angiogenesis and apoptosis in patients with glioma

Variantes genéticas relacionadas à angiogênese e apoptose em pacientes com glioma
Maria Clara Jessica Calastri
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
,
Nicolas Luz Toledo Ortega Rodrigues
2   Universidade do Estado de São Paulo, Campus Júlio de Mesquita Filho, São Paulo SP, Brasil;
,
Gabriela Hatori
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
,
Michele Lima Gregório
3   Universidade de Franca, Franca SP, Brasil;
,
Camila Ive Ferreira Oliveira Brancati
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
,
Eliane Milharcix Zanovelo
4   Faculdade de Medicina de São José do Rio Preto, Hospital de Base, São José do Rio Preto SP, Brasil;
,
José Roberto Lopes Ferraz Filho
4   Faculdade de Medicina de São José do Rio Preto, Hospital de Base, São José do Rio Preto SP, Brasil;
,
Cassiano Merussi Neiva
3   Universidade de Franca, Franca SP, Brasil;
,
Antonio Carlos Ponde Rodrigues Junior
4   Faculdade de Medicina de São José do Rio Preto, Hospital de Base, São José do Rio Preto SP, Brasil;
,
Moacir Fernandes de Godoy
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
,
Carmen Lucia Penteado Lancelloti
5   Faculdade de Ciências Médias da Salta Casa de São Paulo, Departamento de Ciências Patológicas, São Paulo SP, Brasil.
,
Waldir Antonio Tognola
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
,
Dorotéia Rossi Silva Souza
1   Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto SP, Brasil;
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease.

Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%.

Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711).

Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

RESUMO

Introdução Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]).

Métodos 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05.

Resultados Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711).

Conclusões As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doença. O tratamento com TMZ + RT mostrou aumento na sobrevida dos pacientes.

central nervous system - genes, erbB-1 - glioblastoma
sistema nervoso central - genes erbB-1 - glioblastoma

Support

This study was funded by CNPq (1 PhD scholarship) and FAPERP (2 scholarships for scientific initiation).




Publication History

Received: 05 June 2017

Accepted: 16 March 2018

Article published online:
25 August 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Gao X, Tang YJ, Zhang GF, Yu L, Qi ST. ERCC2 rs13181 polymorphism association with glioma susceptibility in a Chinese population. Genet Mol Res 2016; 15(2). doi: 10.4238/gmr.15027585
  • 2 Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131(6):803-820. doi:10.1007/s00401-016-1545-1
  • 3 J. Ferlay, I. Soerjomataram, M. Ervik, R. Dikshit, S. Eser, C. Mathers, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. 2013. http://globocan.iarc.fr. Accessed 21 March 2016
  • 4 Piñeros M, Sierra MS, Izarzugaza MI, Forman D. Descriptive epidemiology of brain and central nervous system cancers in Central and South America. Cancer Epidemiol 2016;44 Suppl 1:S141-S149. doi:10.1016/j.canep.2016.04.007
  • 5 Zhang Y, Pan Y, Li X. Glioblastoma multiforme in the brainstem in a young adult. Clin Neurol Neurosurg 2014;(124):175-178. doi:10.1016/j.clineuro.2014.06.039
  • 6 Walsh KM, Ohgaki H, Wrensch MR. Epidemiology. Handb Clin Neurol 2016;134:3-18. doi: 10.1016/B978-0-12-802997-8.00001-3
  • 7 Zeng T, Cui D, Gao L. Glioma: an overview of current classifications, characteristics, molecular biology and target therapies. Front Biosci 2015; 1(20):1104-1115
  • 8 INCA (2016). Title of subordinate document. In: Estimativa 2016 Incidência de Câncer no Brasil. Instituto Nacional de Cancêr José Alencar Gomes da Silva. http://www.inca.gov.br/estimativa/2016/sintese-de-resultados-comentarios.asp, 2016. Accessed 21 March 2016
  • 9 Pineros M, Gamboa O, Hernandez-Suarez G, Pardo C, Bray F. Patterns and trends in cancer mortality in Colombia 1984–2008, Cancer Epidemiol 2013;37(3)233–239. doi:http://dx.doi.org/10.1016/j.canep.2013.02.003
  • 10 Zhang J, Yang J, Chen Y, Mao Q, Li S, et al. Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population: a Case-Control Study. Mol Neurobiol 2016;53(4):2610-2618. doi: 10.1007/s12035-015-9240-0.
  • 11 He C, Zheng L, Xu Y, Liu M, Li Y, Xu J. Highly sensitive and noninvasive detection of epidermal growth factor receptor T790M mutation in non-small cell lung cancer. Clin Chim Acta 2013;425:119-124. doi:10.1016/j.cca.2013.07.012
  • 12 Di Stefano AL, Labussiere M, Lombardi G, Eoli M, Bianchessi D, Pasqualetti F, et al. VEGFA SNP rs2010963 is associated with vascular toxicity in recurrent glioblastomas and longer response to bevacizumab. J Neurooncol 2015;121(3):499-504. doi:10.1007/s11060-014-1677-x
  • 13 Li B, Zhao W, Li J, Yan M, Xie Z, Zhu Y, et al. Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients. Oncotarget 2016;7(39):63054-63064. doi: 10.18632/oncotarget.10666
  • 14 Salazar LA, Hirata MH, Cavalli SA, Machado MO, Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem 1998;44(8 Pt 1):1748-1750
  • 15 Wang X, Zhang H, Wang D, Li X. Association of genetic polymorphisms of EGFR with glioma in a Chinese population. Genet Test Mol Biomarkers 2015;19(1):59-62. doi:10.1089/gtmb.2014.0228
  • 16 de Mello RA, Ferreira M, Soares-Pires F, Costa S, Cunha J, Oliveira P, et al. The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 Loci on the risk and prognosis of portuguese patients with non-small cell lung cancer. PLoS One 2013;8(9):e72373. doi:10.1371/journal.pone.0072373
  • 17 Octavio-Aguilar P, Ramos-Frías J. Aplicación de la genética de poblaciones en el ámbito de la medicina. Biomedica 2014;34(2):171-179. doi:10.1590/S0120-41572014000200004
  • 18 Xu J, Turner A, Little J, Bleecker ER, Meyers DA. Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: hint for genotyping error? Hum Genet 2002;111(6):573-574
  • 19 Wibom C, Ghasimi S, Van Loo P, Brännström T, Trygg J, Lau C, et al. EGFR gene variants are associated with specific somatic aberrations in glioma. PLoS One 2012;7(12):e47929. doi: 10.1371/journal.pone.0047929
  • 20 Hansen TF, Jakobsen A. Clinical implications of genetic variations in the VEGF system in relation to colorectal cancer. Pharmacogenomics 2011;12(12):1681–1693. doi:10.2217/pgs.11.118
  • 21 Beeghly-Fadiel A, Shu XO, Lu W, Long J, Cai Q, Xiang YB, et al. Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study. Cancer Epidemiol Biomarkers Prev 2011;20(1):33-41. doi:10.1158/1055-9965.EPI-10-0793
  • 22 Hu Y, Chen F, Liu F, Liu X, Huang N, Cai X, et al. Overexpression of TIP30 inhibits the growth and invasion of glioma cells. Mol Med Rep 2016;13(1):605-612. doi:10.3892/mmr.2015.4619
  • 23 Akkiz H, Bayram S, Bekar A, Akgollu E, Ozdil B. Cyclin d1 g870a polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study. Cancer Epidemiol 2010;34(3):298–302. doi:10.1016/j.canep.2010.02.011
  • 24 Li HX, Peng XX, Zong Q, Zhang K, Wang MX, et al. Cigarette smoking and risk of adult glioma: a meta-analysis of 24 observational studies involving more than 2.3 million individuals. Onco Targets Ther 2016;(9):3511-3523. doi: 10.2147/OTT.S99713
  • 25 Koukourakis MI, Mitrakas AG, Giatromanolaki A. Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: evidence and issues to resolve. Br J Cancer 2016;114(5):485-496. doi:10.1038/bjc.2016.19