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A New Insight for the Identification of Oncogenic Variants in Breast and Prostate Cancers in Diverse Human Populations, With a Focus on Latinos
Journal
Frontiers in Pharmacology
ISSN
1663-9812
Date Issued
2021-04-12
Author(s)
Nelson M. Varela
Patricia Guevara-Ramírez
Cristian Acevedo
Tomás Zambrano
Isaac Armendáriz-Castillo
Santiago Guerrero
Luis A. Quiñones
Andrés López-Cortés
DOI
10.3389/fphar.2021.630658
Abstract
<jats:p><jats:bold>Background:</jats:bold> Breast cancer (BRCA) and prostate cancer (PRCA) are the most commonly diagnosed cancer types in Latin American women and men, respectively. Although in recent years large-scale efforts from international consortia have focused on improving precision oncology, a better understanding of genomic features of BRCA and PRCA in developing regions and racial/ethnic minority populations is still required.</jats:p><jats:p><jats:bold>Methods:</jats:bold> To fill in this gap, we performed integrated <jats:italic>in silico</jats:italic> analyses to elucidate oncogenic variants from BRCA and PRCA driver genes; to calculate their deleteriousness scores and allele frequencies from seven human populations worldwide, including Latinos; and to propose the most effective therapeutic strategies based on precision oncology.</jats:p><jats:p><jats:bold>Results:</jats:bold> We analyzed 339,100 variants belonging to 99 BRCA and 82 PRCA driver genes and identified 18,512 and 15,648 known/predicted oncogenic variants, respectively. Regarding known oncogenic variants, we prioritized the most frequent and deleterious variants of BRCA (<jats:italic>n</jats:italic> = 230) and PRCA (<jats:italic>n</jats:italic> = 167) from Latino, African, Ashkenazi Jewish, East Asian, South Asian, European Finnish, and European non-Finnish populations, to incorporate them into pharmacogenomics testing. Lastly, we identified which oncogenic variants may shape the response to anti-cancer therapies, detailing the current status of pharmacogenomics guidelines and clinical trials involved in BRCA and PRCA cancer driver proteins.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> It is imperative to unify efforts where developing countries might invest in obtaining databases of genomic profiles of their populations, and developed countries might incorporate racial/ethnic minority populations in future clinical trials and cancer researches with the overall objective of fomenting pharmacogenomics in clinical practice and public health policies.</jats:p>