Browsing by Author "Munoz, Cesar"

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    Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses
    (2025) Gonzalez, Constanza; Garcia-Perez, Alfonso; Nervi, Bruno; Munoz, Cesar; Morales, Erik; Losada, Hector; Merino-Pereira, Gina; Rothhammer, Francisco; Bermejo, Justo Lorenzo
    Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.
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    Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country
    (2023) Boekstegers, Felix; Scherer, Dominique; Barahona Ponce, Carol; Marcelain, Katherine; Garate-Calderon, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, Cesar; Retamales, Javier; de Toro, Gonzalo; Barajas, Olga; Rivera, Maria Teresa; Cortes, Analia; Loader, Denisse; Saavedra, Javiera; Gutierrez, Lorena; Ortega, Alejandro; Bertran, Maria Enriqueta; Bartolotti, Leonardo; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisan, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Hector; Almau, Mauricio; Fernandez, Plinio; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Catira; Acuna-Alonzo, Victor; Gallo, Carla; Linares, Andres Ruiz; Rothhammer, Francisco; Lorenzo Bermejo, Justo
    Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.
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    Disturbance and the (surprising?) role of ecosystem engineering in explaining spatial patterns of non-native plant establishment
    (2021) Root-Bernstein, Meredith; Munoz, Cesar; Armesto, Juan
    Different conceptions of disturbance differ in the degree to which they appeal to mechanisms that are general and equivalent, or species-, functional group-, or interaction-specific. Some concepts of disturbance, for example, predict that soil disturbances and herbivory have identical impacts on species richness via identical mechanisms (reduction in biomass and in competition). An alternative hypothesis is that the specific traits of disturbance agents (small mammals) and plants differentially affect the richness or abundance of different plant groups. We tested these hypotheses on a degu (Octodon degus) colony in central Chile. We ask whether native and non-native forbs respond differently to degu bioturbation on runways versus herbivory on grazing lawns. We ask whether this can explain the increase in non-native plants on degu colonies. We found that biopedturbation did not explain the locations of non-native plants. We did not find direct evidence of grazing increasing non-native herbs either, but a grazing effect appears to be mediated by grass, which is the dominant cover. Further, we provide supplementary evidence to support our interpretation that a key mechanism of non-native spread is the formation of dry soil conditions on grazing lawns. Thus, ecosystem engineering (alteration of soil qualities) may be an outcome of disturbances, in which each interacts with specific plant traits, to create the observed pattern of non-native spread in the colony. Based on these results, we propose to extend Jentsch and White (Ecology, 100, 2019, e02734) concept of combined pulse/ disturbance events to the long-term process duality of ecosystem engineering/ disturbance.
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    Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
    (2022) Blandino, Alice; Scherer, Dominique; Rounge, Trine B.; Umu, Sinan U.; Boekstegers, Felix; Barahona Ponce, Carol; Marcelain, Katherine; Garate-Calderon, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, Cesar; Retamales, Javier; de Toro, Gonzalo; Barajas, Olga; Rivera, Maria Teresa; Cortes, Analia; Loader, Denisse; Saavedra, Javiera; Gutierrez, Lorena; Ortega, Alejandro; Bertran, Maria Enriqueta; Gabler, Fernando; Campos, Monica; Alvarado, Juan; Moisan, Fabrizio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel E.; Losada, Hector; Almau, Mauricio; Fernandez, Plinio; Gallegos, Ivan; Olloquequi, Jordi; Fuentes-Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Catira; Gallo, Carla; Linares, Andres Ruiz; Rothhammer, Francisco; Lorenzo Bermejo, Justo
    Simple Summary Gallbladder cancer (GBC) is an aggressive disease with poor prognosis that urgently needs risk biomarkers for prevention. Long noncoding RNAs (lncRNAs) have been linked to various types of cancer and have good potential as circulating biomarkers. Prediction of lncRNA expression based on genotype data may contribute to quantify individual GBC risk even without direct lncRNA expression measurement. In this study, we investigate the relationship between GBC risk and genotype-based expression of circulating lncRNAs. Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones -> dysplasia -> GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r(2) = 0.26) and three cis-C22orf34-eQTLs (r(2) = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.