Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population

Simple item page
dc.article.number561
dc.catalogadoryvc
dc.contributor.authorOwen, Gareth Ivor
dc.contributor.authorCórdova-Delgado, Miguel
dc.contributor.authorBustos, Bernabé I.
dc.contributor.authorCerpa Castro, Leslie
dc.contributor.authorGonzález Hevia, Pamela Andrea
dc.contributor.authorMorales-Pison, Sebastián
dc.contributor.authorGarcía-Bloj, Benjamín
dc.contributor.authorGarrido, Marcelo
dc.contributor.authorMiquel, Juan Francisco
dc.contributor.authorQuiñones, Luis A.
dc.date.accessioned2024-04-29T16:56:08Z
dc.date.available2024-04-29T16:56:08Z
dc.date.issued2024
dc.date.issued2024
dc.description.abstractBackground: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry. Methods: To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with p ≤ 0.05 and Bonferroni’s multiple adjustment tests determined statistical differences between allele frequencies. Results: Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase (DPYD) variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 (NUDT15) rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of TMPT gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031–0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene (UGT1A1) rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations. Conclusions: This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.
dc.fechaingreso.objetodigital2024-04-29
dc.fuente.origenORCID
dc.identifier.doi10.3390/pharmaceutics16040561
dc.identifier.urihttps://doi.org/10.3390/pharmaceutics16040561
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/85365
dc.information.autorucFacultad de Ciencias Biológicas; Owen Gareth Ivor; 0000-0003-3807-6054; 1000459
dc.information.autorucFacultad de Ciencias Biológicas; González Hevia, Pamela Andrea; 0009-0001-4402-2020; 127012
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final18
dc.pagina.inicio1
dc.revistaPharmaceutics
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 Atribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPharmacogenetic
dc.subjectSingle-nucleotide
dc.subjectPolymorphisms
dc.subjectAnticancer
dc.subjectLatin American
dc.subjectMapuche-Huilliche
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.titleAssessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population
dc.typeartículo
dc.volumen16
sipa.codpersvinculados1000459
sipa.codpersvinculados127012
sipa.trazabilidadORCID;2024-04-29
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
TEXTO COMPLETO_Assessing the Occurrence and Influence of Cancer.pdf
Size:
1 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas