Abstract
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 in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in 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 of AGT, MGMT, and TP53 from 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 in AGT (OR 2.74, 1.40–5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17–10.10 95% CI), and rs4968187 in TP53 (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 the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.
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Data Availability
The VCF files from Mexican patients can be accessed in Zenodo (https://zenodo.org/). Identifier: https://doi.org/10.5281/zenodo.3737200.
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Acknowledgements
We thank Patricia Rosas, Laura Márquez, and Patricia de la Torre for their contributions in the project.
Funding
This study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (Salud-2013-01-202720 to TWO, Scholarship number 969754 to JACE).
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SIMP, APP, NRN, SVM, TWO, and POW involved in conceptualization of the study. TWO, BCD, and POW designed the study. XB, KCA, QC, SIMP, APP, TESC, TWO, JACE, JLGA, TC, and DM contributed to data acquisition and processing. ESR, RGB, POW, TESC, LSG, SVM, LTC, OG, RMAG performed data validation. JACE, LGFR, and TWO participated in statistical analysis. LGFR and TWO contributed to validation of results. All authors interpreted the results and involved in reviewing and editing. JACE and TWO involved in writing of the manuscript..
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Carlos-Escalante, J.A., Gómez-Flores-Ramos, L., Bian, X. et al. Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma. Cell Mol Neurobiol 41, 1285–1297 (2021). https://doi.org/10.1007/s10571-020-00901-7
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DOI: https://doi.org/10.1007/s10571-020-00901-7