Browsing by Author "Owen, Gareth I."
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Item A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer(2021) Cordova-Delgado, Miguel; Bravo, María Loreto; Cumsille, Elisa; Hill, Charlotte N.; Muñoz-Medel, Matías; Pinto, Mauricio P.; Retamal, Ignacio N.; Lavanderos, María A.; Miquel, Juan Francisco; Rodriguez-Fernandez, Maria; Liao, Yuwei; Li, Zhiguang; Corvalán, Alejandro H.; Armisén, Ricardo; Garrido, Marcelo; Quiñones, Luis A.; Owen, Gareth I.Background: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity. Methods: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results: Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.Item A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability(MDPI, Basel Sz., 2020) Pinto, Mauricio; Córdova-Delgado, Miguel; Retamal, Ignacio; Muñoz-Medel, Matías; Bravo, Loreto; Durán, Doris; Villanueva, Francisco; Sánchez, César; Acevedo, Francisco; Mondaca, Sebastián; Érica, Koch; Ibáñez, Carolina; Galindo, Héctor; Madrid, Jorge; Nervi, Bruno; Peña, José; Torres, Javiera; Garrido, Marcelo; Owen, Gareth I.; Corvalán, Alejandro H.; Armisén, RicardoGastric cancer (GC) is a complex and heterogeneous disease. In recent decades, The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) defined GC molecular subtypes. Unfortunately, these systems require high-cost and complex techniques and consequently their impact in the clinic has remained limited. Additionally, most of these studies are based on European, Asian, or North American GC cohorts. Herein, we report a molecular classification of Chilean GC patients into five subtypes, based on immunohistochemical (IHC) and in situ hybridization (ISH) methods. These were Epstein–Barr virus positive (EBV+), mismatch repair-deficient (MMR-D), epithelial to mesenchymal transition (EMT)-like, and accumulated (p53+) or undetected p53 (p53−). Given its lower costs this system has the potential for clinical applicability. Our results confirm relevant molecular alterations previously reported by TCGA and ACRG. We confirm EBV+ and MMR-D patients had the best prognosis and could be candidates for immunotherapy. Conversely, EMT-like displayed the poorest prognosis; our data suggest FGFR2 or KRAS could serve as potential actionable targets for these patients. Finally, we propose a low-cost step-by-step stratification system for GC patients. To the best of our knowledge, this is the first Latin American report on a molecular classification for GC. Pending further validation, this stratification system could be implemented into the routine clinicPublication Quadruple therapies show a higher eradication rate compared to standard triple therapy for Helicobacter pylori infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries(2024) Medel-Jara, Patricio; Reyes Placencia, Diego; Fuentes-López, Eduardo; Corsi, Oscar; Latorre, Gonzalo; Antón, Rosario; Jiménez, Elena; Miralles-Marco, Ana; Caballero, Carmelo; Boggino, Hugo; Cantero, Daniel; Barros, Rita; Santos-Antunes, João; Díez, Marc; Quiñones, Luis A.; Riquelme, Erick; Rollan, Antonio; Cerpa, Leslie C.; Valdés, Ivania; Nyssen, Olga P.; Moreira, Leticia; Gisbert, Javier P.; Camargo, M. Constanza; Ortiz-Olvera, Nayeli; Leon‐Takahashi, Alberto, M.; Ruiz-Garcia, Erika; Fernández-Figueroa, Edith A.; Garrido, Marcelo; Owen, Gareth I.; Cervantes, Andrés; Fleita, Tania; Riquelme, ArnoldoIntroduction: Gastric cancer (GC) is one of the most lethal malignancies worldwide.Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces therisk of developing this neoplasia. There is extensive evidence regarding quadrupletherapy with relevance to the European population. However, in Latin America, dataare scarce. Furthermore, there is limited information about the eradication ratesachieved by antibiotic schemes in European and Latin American populations.Objective: To compare the effectiveness of standard triple therapy (STT), quadrupleconcomitant therapy (QCT), and bismuth quadruple therapy (QBT) in six centers inEurope and Latin America.Methods: A retrospective study was carried out based on the LEGACy registry from2017 to 2022. Data from adult patients recruited in Portugal, Spain, Chile, Mexico,and Paraguay with confirmed H. pylori infection who received eradication therapyand confirmatory tests at least 1 month apart were included. Treatment success by each scheme was compared using a mixed multilevel Poisson regression, adjustingfor patient sex and age, together with country‐specific variables, including preva-lence of H. pylori antibiotic resistance (clarithromycin, metronidazole, and amoxi-cillin), and CYP2C19 polymorphisms.Results: 772 patients were incorporated (64.64% females; mean age of 52.93 years).The total H. pylori eradication rates were 75.20% (255/339) with STT, 88.70% (159/178) with QCT, and 91.30% (191/209) with QBT. Both quadruple therapies (QCT‐QBT) showed significantly higher eradication rates compared with STT, with anadjusted incidence risk ratio (IRR) of 1.25 (p: <0.05); and 1.24 (p: <0.05), respectively.The antibiotic‐resistance prevalence by country, but not the prevalence of CYP2C19polymorphism, showed a statistically significant impact on eradication success.Conclusions: Both QCT and QBT are superior to STT for H. pylori eradication whenadjusted for country‐specific antibiotic resistance and CYP2C19 polymorphism in asample of individuals residing in five countries within two continents.