Browsing by Author "Bustamante, Alberto"
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Item Adaptation to Extreme Environments in an Admixed Human Population from the Atacama Desert(2019) Vicuña, Lucas; Fernández, Mario; Vial, Cecilia; Valdebenito, Patricio; Chaparro, Eduardo; Espinoza, Karena; Ziegler, Annmarie; Bustamante, Alberto; Eyheramendy, SusanaInorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels(upto600 mg/l)in drink ing water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (120 mg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests—PBSn1 and an ancestry-enrichment test—in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P1⁄4 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P1⁄4 1.3 109 ) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.Publication Comparative Analysis of Very Reduced vs Full Dose BCG Treatment for High-RiskNon-Muscle Invasive Bladder Cancer:A Contemporary Experience from Chile(2023) Grajales, Valentina; Contieri, Roberto; Tan, Wei Shen; Flores, Marta; Schultz, Marcela; Pinochet, Rodrigo; Bustamante, Alberto; Kamat, Ashish; Mario Fernandez; Fernández Arancibia, MarioBACKGROUND:Adjuvant bacillus Calmette-Gu ́erin (BCG) is recommended for high-risk (HR) non-muscle invasivebladder cancer (NMIBC), but BCG shortages have led to exploration of reduced-dose regimens and shortened maintenancedurations out of necessity, with limited data on treatment efficacy in Latin America.OBJECTIVE:Oncological outcomes of HR-NMIBC patients treated with reduced (RD,1/4th dose) vs full dose (FD) BCGinstillations ofDanish Strain1331 BCG.METHODS:We performed a retrospective study of HR-NMIBC patients treated with BCG between 2003 and 2022 at ourcenter in Santiago Chile. We stratified patients according to either RD (1/4th dose) or FD BCG. Univariate and multivariableCox regression models were used to predict recurrence. Kaplan-Meier method was used to calculate survival estimates.RESULTS:Of a total of 200 patients, 116 (58%) had RD and 84 (42%) FD BCG. Median follow-up was 57 months (IQR:29–100). Patients who received FD BCG had a lower risk of recurrence (HR: 0.41, 95% CI 0.22–0.74) and high-grade(HG)-recurrence (HR: 0.30, 95% CI 0.15–0.61;p= 0.001). More patients in the RD vs FD group progressed to MIBC (10/84vs 2/116;p= 0.18). Additionally, patients were less likely to stop BCG treatment in the RD group compared to the FD groupdue to toxicity (5% vs 11%,p= 0.14).CONCLUSIONS:A 1/4th dose ofDanish Strain1331 BCG treatment was associated with worse recurrence free rate andHG-recurrence rate in our cohort. Patients with RD had lower discontinuation treatment rates due to a reduced toxicity profile.These findings would suggest that RD BCG would compromise oncological outcomes in HR-NMIBC patients.Item Impact of arsenic exposure on clinicopathological characteristics of bladder cancer: A comparative study between patients from an arsenic-exposed region and nonexposed reference sites(Elsevier Inc., 2020-02) Fernández, Mario; Valdebenito, Patricio; Delgado, Iris; Segebre, Jorge; Chaparro, Eduardo; Fuentealba, David; Castillo, Martín; Vial, Cecilia; Barroso, Juan; Ziegler, Annemarie; Bustamante, AlbertoBackground: Beyond exposure to arsenic in drinking-water, there is few information about demographic and clinicopathological features of patients with bladder cancer living in arsenic-exposed regions. The aim of the study was to assess the impact of arsenic exposure on clinicopathological characteristics in patients with bladder cancer from a contaminated region compared to those of 2 reference areas. Methods: Data of 285 patients with bladder cancer (83 with arsenic exposure from Antofagasta and 202 controls from 2 different sites in Santiago) were obtained through personal interviews and from review of medical records. Demographic, clinicopathological parameters, and information on relevant environmental risk factors were compared with parametric and nonparametric tests as needed. Multivariable analysis was performed to identify independent predictors for high grade and muscle-invasive disease (T2-4). Results: We found no significant differences between groups regarding age at presentation (66.4 vs. 66.5 and 67.2 years; P = 0.69, for exposed vs. the 2 nonexposed groups, respectively) and female gender (28.9% vs. 29.8% and 26.2%; P = 0.84). Proportion of current smokers was significantly lower in the exposed population (10.7% vs. 38.6% and 26.9%; P < 0.001). There was a significantly higher proportion of locally advanced (10.8 vs. 1.8 and 0.7% T3/4; P = 0.002) and high-grade tumors (79.5% vs. 63.2% and 64.1%; P = 0.001) within arsenic-exposed patients. Arsenic exposure was the only significant predictor for the presence of high-grade tumors (adjusted OR: 5.10; 95%CI: 2.03-12.77) on multivariable analysis. Conclusions: Our study revealed relevant clinical differences in bladder cancer patients with a history of arsenic exposure as compared to nonexposed cases. The more aggressive phenotype associated to arsenic-related bladder cancer should be considered when designing efficient screening strategies for this high-risk population.