Browsing by Author "Córdova-Delgado, Miguel"

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    Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population
    (2024) Owen, Gareth Ivor; Córdova-Delgado, Miguel; Bustos, Bernabé I.; Cerpa Castro, Leslie; González Hevia, Pamela Andrea; Morales-Pison, Sebastián; García-Bloj, Benjamín; Garrido, Marcelo; Miquel, Juan Francisco; Quiñones, Luis A.
    Background: 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.
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    Contrast-enhanced mammography predicts pathological response after neoadjuvant chemotherapy in locally advanced breast cancer
    (2022) Canteros, Daniel; Walbaum, Benjamin; Córdova-Delgado, Miguel; Torrealba, Andrés; Reyes, Constanza; Navarro, María Elena; Razmilic, Dravna; Camus, Mauricio; Dominguez, Francisco; Navarrete, Orieta; Pinto, Mauricio P.; Pizarro, Gonzalo; Acevedo, Francisco; Sánchez, César
    Introduction: Recently, contrast-enhanced mammography (CEM) has emerged as a reliable alternative to breast magnetic resonance imaging (MRI) for the assessment of pathological response in breast cancer patients. Our study sought to determine the diagnostic accuracy of CEM to predict pathological complete response (pCR) in patients who received neoadjuvant chemotherapy (NACT). Methods: We retrieved the medical records of patients who underwent NACT at our institution. Using post-surgery pCR, morphological evidence and CEM enhancement tumours were classified as follows: 1) radiologic complete response (rCR); 2) functional radiological complete response (frCR); and 3) non-complete response. Initially, we used multivariate analyses adjusted by clinical variables and frCR or rCR to determine which variables affected pathological response. Then, CEM diagnostic accuracy to discriminate pCR was assessed using receiver operating characteristic curves in univariate and multivariate models including either frCR or rCR. Results: A total of 48 patients were included in our study. Most patients (68.7%) were hormone receptor (HR)+ and 41.6% (20) of the patients achieved pCR. Using univariate logistic regression analyses we found that HR status, HER2 status, rCR and frCR had a significant impact on CEM diagnostic accuracy. Exploratory analyses found that CEM sensitivity was higher for HR− tumours. Multivariate logistic regression analyses found 60% sensitivity, 92.9% specificity and 79.2% accuracy in a model that included clinical variables and rCR. Conclusion: CEM is a reliable alternative to high-cost, time-consuming breast MRI that predicts pCR in patients undergoing NACT; CEM diagnostic accuracy was higher among patients who harboured HR− tumours.