Implementation of a Pharmacogenomic Program in a Brazilian Public Institution

Abstract

This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs – fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost–effectiveness.

Frequency of DPYD gene variants and phenotype inference in a Southern Brazilian population

“…These frequencies are higher than the ones found in our sample (0.25% and 0%, respectively) which is in agreement with the differences observed across the country. Additionally, rs67376798 was analyzed in a sample from the Southeast and the authors described a frequency of 1% for this variant in a sample composed by 50 tumor tissues (Suarez-Kurtz et al, 2020). Moreover, the variant was present in 4% of a sample composed by Native Americans from the North, which is 10-fold higher than the frequency described in this study (0.38%).…”

“…To our knowledge, other six Brazilian studies analyzed rs3918290 (Barra et al, 2014;Bonifaz-Peña et al, 2014;de Castro et al, 2020;Galarza et al, 2016;Rodrigues et al, 2019;Suarez-Kurtz et al, 2020) and four studies analyzed rs55886062 (Bonifaz-Peña et al, 2014;Galarza et al, 2016;Rodrigues et al, 2019;Suarez-Kurtz et al, 2020) including one that was based in a sample from the South region (n = 60); however, they did not find any carrier of the variants, except for two studies. The first one reported a frequency of 1% and 2%, respectively, in a Native American population from the North of Brazil (Rodrigues et al, 2019).…”

Dihydropyrimidine dehydrogenase (DPD) polymorphisms knocking on the door

“…As Brazil is a large country with great ethnic diversity, DPYD allele frequencies are not homogeneous across its subpopulations and studies with specific subpopulations show different allele prevalence. In example, data from 146 individuals from three Amazonian Amerindian populations showed minor allele frequencies of 1% and 2% for DPYD*2A and DPYD*13, and in healthy Brazilians of predominantly African ancestry or self-reported as black the c.557A>G variant was detected at a frequency of 2.6% [ 35 , 36 ]. For further analysis and discussions in the text, data from the ABraOM repository will be used as a parameter.…”

Pharmacogenomic tests in Oncology – finding the right dose

“…In this issue of Brazilian Journal of Oncology (BJO), Suarez-Kurtz discusses the pharmacogenetics/ genomics (PGx) anticancer drug-testing program developed by his group at the Brazilian National Cancer Institute (INCA). (1) Drug -gene pairs were selected for PGx testing based on the presence of clinically validated PGx associations and the availability of international guidelines with PGx-informed dosing recommendations. Fluoropyrimidines-DPYD, irinotecan-UGT1A1, and thiopurines-TPMT/NUDT15 were initially included in the evaluation.…”

“…In cancer patients, genome variations, as well as somatically acquired genome variants, can influence the antitumor and/ or toxic effect of therapeutic agents. (1) Most human disorders, including cancer, may be influenced by different genes and genetic variants. Likewise, pharmacokinetics and pharmacological effects of therapeutic agents can be determined by genes encoding drug-metabolizing enzymes, transporters, targets, and disease-modifying genes.…”