Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma
Por:
Carlos-Escalante J.A., Gomez-Flores-Ramos, Liliana, Bian, Xiaopeng, Perdomo-Pantoja, Alexander, de Andrade, Kelvin Cesar, Mejía-Pérez S.I., Cacho-Diaz, Bernardo, Gonzalez-Barrios, Rodrigo, Reynoso-Noveron, Nancy, Soto-Reyes, Ernesto, Sánchez-Correa T.E., Guerra-Calderas, Lissania, Yan, Chunhua, Chen, Qingrong, Castro-Hernandez, Clementina, Vidal-Millan, Silvia, Taja-Chayeb, Lucia, Gutierrez, Olga, Álvarez-Gómez R.M., Gómez-Amador J.L., Ostrosky-Wegman, Patricia, Mohar-Betancourt, Alejandro, Herrera-Montalvo L.A., Corona, Teresa, Meerzaman, Daoud, Wegman-Ostrosky, Talia
Publicada:
1 ago 2021
Ahead of Print:
1 jun 2020
Resumen:
Astrocytoma is the most common type of primary brain tumor. The risk
factors for astrocytoma are poorly understood; however, germline genetic
variants account for 25% of the risk of developing gliomas. In this
study, we assessed the risk of astrocytoma associated with variants
inAGT, known by its role in angiogenesis,TP53, a well-known tumor
suppressor and the DNA repair geneMGMTin a Mexican population. A
case-control study was performed in 49 adult Mexican patients with grade
II-IV astrocytoma. Sequencing of exons and untranslated regions
ofAGT,MGMT, andTP53from was carried in an Ion Torrent platform.
Individuals with Mexican Ancestry from the 1000 Genomes Project were
used as controls. Variants found in our cohort were then assessed in a
The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort.
Variants rs1926723 located inAGT(OR 2.74, 1.40-5.36 95% CI), rs7896488
inMGMT(OR 3.43, 1.17-10.10 95% CI), and rs4968187 inTP53(OR 2.48,
1.26-4.88 95% CI) were significantly associated with the risk of
astrocytoma after multiple-testing correction. This is the first study
where theAGTrs1926723 variant,TP53rs4968187, andMGMTrs7896488 were found
to be associated with the risk of developing an astrocytoma.
Filiaciones:
Carlos-Escalante J.A.:
PECEM (MD/PhD), Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico
Gomez-Flores-Ramos, Liliana:
Cátedras CONACYT- Instituto Nacional de Salud Pública, Cuernavaca, Morelos 62100, Mexico
Bian, Xiaopeng:
Computational Genomics and Bioinformatics Group, Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20850, United States
Perdomo-Pantoja, Alexander:
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
de Andrade, Kelvin Cesar:
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD 20850, United States
Mejía-Pérez S.I.:
Departamento de Enseñanza, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, 13269, Mexico
Departamento de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”, Mexico City, 14269, Mexico
Cacho-Diaz, Bernardo:
Unidad de Neurociencia, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Gonzalez-Barrios, Rodrigo:
Dirección de Investigación, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Reynoso-Noveron, Nancy:
Dirección de Investigación, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Soto-Reyes, Ernesto:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa, Mexico City, 05370, Mexico
Sánchez-Correa T.E.:
Departamento de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”, Mexico City, 14269, Mexico
Guerra-Calderas, Lissania:
Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana-Cuajimalpa, Mexico City, 05370, Mexico
Yan, Chunhua:
Computational Genomics and Bioinformatics Group, Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20850, United States
Chen, Qingrong:
Computational Genomics and Bioinformatics Group, Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20850, United States
Castro-Hernandez, Clementina:
Unidad de Epidemiología e Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, UNAM-INCAN, Mexico City, 14080, Mexico
Vidal-Millan, Silvia:
Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Taja-Chayeb, Lucia:
Dirección de Investigación, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Gutierrez, Olga:
Dirección de Investigación, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Álvarez-Gómez R.M.:
Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
Gómez-Amador J.L.:
Departamento de Neurocirugía, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”, Mexico City, 14269, Mexico
Ostrosky-Wegman, Patricia:
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, 04510, Mexico
Mohar-Betancourt, Alejandro:
Unidad de Epidemiología e Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, UNAM-INCAN, Mexico City, 14080, Mexico
Herrera-Montalvo L.A.:
Unidad de Epidemiología e Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, UNAM-INCAN, Mexico City, 14080, Mexico
Dirección General, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
Corona, Teresa:
Laboratorio Clínico de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez”, Mexico City, 14269, Mexico
Meerzaman, Daoud:
Computational Genomics and Bioinformatics Group, Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20850, United States
Wegman-Ostrosky, Talia:
Dirección de Investigación, Instituto Nacional de Cancerología, Mexico City, 14080, Mexico
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