Prevalence of actionable pharmacogenomic variants in Brazilian patients with cancer.
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Schuch Jaqueline B, Botton Mariana R, De Baumont Angélica C, Curzel Giovana, Cadore Nathan A, Bordignon Cláudia, Rosa Mahira L, Vasconcellos Vitor F, Barros Lilian A R, Souza Cristiano P, Barra Williams F, Louzeiro Daniela L C, Notari Alessandra, de Menezes Juliana J, Liedke Pedro E R, Bertollo Gláucio A, Gongora Aline B L, Ascenco Henrique G, Kowalski-Neto Eduardo, Oppermann Christina P, Werutsky Gustavo, Santos Edilmar M, Brandão Flavio S, Freitas-Junior Ruffo, Nogueira-Rodrigues Angélica, Mancini André L C, Bessel Marina, Macedo Gabriel S, Rosa Daniela D
Аннотация
METHODS: This analysis included 452 patients (259 BC, 193 MPC) from a multicenter study across 19 Brazilian sites. Exome sequencing was performed, and PGx variants were analyzed using the Pharmacogenomics Clinical Annotation Tool (PharmCAT) following the Clinical Pharmacogenetics Implementation Consortium (CPIC®) guidelines. Genotypes, star alleles, and predicted phenotypes were reported for 15 clinically relevant pharmacogenes.
RESULTS: Actionable PGx phenotypes were detected in 99.33% of participants. The decreased-function ABCG2 rs2231142 T allele occurred at 8.96%, and the VKORC1 rs9923231 T allele at 32.63%. In SLCO1B1, normal function predominated (63.11%), with 21.11% exhibiting decreased function. Normal metabolizer phenotypes were most frequent in CYP2C19 (45.35%), CYP2C9 (70.51%), and CYP3A4 (94.62%), whereas CYP2B6 was dominated by intermediate metabolizers (43.02%) and CYP3A5 by poor/intermediate metabolizers (93.79%). Normal diplotypes predominated in thiopurine-related genes (NUDT15: 92.92%; TPMT: 88.72%), although nonfunctional alleles were observed. In UGT1A1, decreased-function alleles accounted for approximately 37% of participants. Clinically relevant DPYD and RYR1 variants were rare (<2.0%).
CONCLUSION: Nearly all Brazilian patients with cancer carried at least one actionable PGx variant, highlighting the potential impact of PGx-guided therapy in oncology. These results underscore the value of integrating pharmacogenomic strategies into clinical practice in Brazil.