Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma

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.