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Assessing the impact of a single qualitative fecal immunochemical test on colonoscopy prioritization and mortality in risk-stratified patients with suspected colorectal cancer: a retrospective cohort study
(Elsevier BV, 2025-10)
Felipe F. Quezada-Diaz
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ACEVEDO ROMO, JOHANNA PATRICIA
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Maite González
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Andrea Tello
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Richard Castillo
2Scopus© Citations 2
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International collaborative research to improve gallbladder cancer prevention
(Springer Science and Business Media LLC, 2025-04-04)
Dominique Scherer
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Rajiv Kumar
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Justo Lorenzo Bermejo
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Carol Barahona Ponce
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Claudio Mengoa
1
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A snapshot of cancer in Chile II: an update on research, strategies and analytical frameworks for equity, innovation and national development
(Springer Science and Business Media LLC, 2024-12-18)
Cristóbal Vacarezza
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Julieta Araneda
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Pamela Gonzalez
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Oscar Arteaga
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Katherine Marcelain
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Introduction</jats:title> <jats:p>Chile has achieved developed nation status and boasts a life expectancy of 81 + years; however, the healthcare and research systems are unprepared for the social and economic burden of cancer. One decade ago, the authors put forward a comprehensive analysis of cancer infrastructure, together with a series of suggestions on research orientated political policy.</jats:p> </jats:sec><jats:sec> <jats:title>Objectives</jats:title> <jats:p>Provide an update and comment on policy, infrastructure, gender equality, stakeholder participation and new challenges in national oncology. Assess the funding and distribution of cancer investigation. Present actions for the development of oncology research, innovation and patient care.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Triangulating objective system metrics of economic, epidemiological, private and public sector resources together with policy analysis, we assessed cancer burden, infrastructure, and investigation. We analyzed governmental and private-sector cancer databases, complemented by interviews with cancer stakeholders.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Governmental policy and patient advocacy have led to the recognition of cancer burden, a cancer law, and a national cancer plan. Cancer has become the leading cause of death in Chile (59,876 cases and 31,440 cancer deaths in 2022), yet only 0.36% gross domestic product (GDP) is directed to research and development. Inequalities in treatment regimens persist. Prevention policy has lowered tobacco consumption, sugar intake via soft drinks and offered a high coverage of HPV vaccines. A high-quality cancer research community is expanding, and internationally sponsored clinical oncology trials are increasing.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The cancer law has facilitated advancement in policy. Prevention policies have impacted tobacco and sugar intake, while gender equality and care inequality have entered the public forum. Cancer research is stagnated by the lack of investment. Implementation of a cancer registry and biobanking, reinforcement of prevention strategies, development of human resources, promotion of clinical trial infrastructure and investment in new technologies must be placed as a priority to permit advancements in innovation and equitable cancer care.</jats:p> </jats:sec>
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Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease
(MDPI AG, 2024-12-17)
Francisco Ceballos
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Felix Boekstegers
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Dominique Scherer
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Carol Barahona Ponce
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Katherine Marcelain
<jats:p>Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual FROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of FROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% FROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans.</jats:p>
1
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SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages
(2024)
Aldo Barrera
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Constanza Martínez-Valdebenito
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Jenniffer Angulo
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Carlos Palma
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HORMAZABAL CASTILLO, JUAN PATRICIO
<jats:p>Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.</jats:p>
5Scopus© Citations 3
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Differential Effects of a Telemonitoring Platform in the Development of Chemotherapy-Associated Toxicity: A Randomized Trial Protocol
(2024)
Felipe Martínez
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Carla Taramasco
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Manuel Espinoza
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ACEVEDO ROMO, JOHANNA PATRICIA
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Carolina Goic
<jats:p>Chemotherapy requires careful monitoring, but traditional follow-up approaches face significant challenges that were highlighted by the COVID-19 pandemic. Hence, exploration into telemonitoring as an alternative emerged. The objective is to assess the impact of a telemonitoring platform that provides clinical data to physicians overseeing solid tumor patients, aiming to enhance the care experience. The methodology outlines a parallel-group randomized clinical trial involving recently diagnosed patients with solid carcinomas preparing for curative intent chemotherapy. Eligible adult patients diagnosed with specific carcinoma types and proficient in Spanish, possessing smartphones, will be invited to participate. They will be randomized using concealed allocation sequences into two groups: one utilizing a specialized smartphone application called Contigo for monitoring chemotherapy toxicity symptoms and accessing educational content, while the other receives standard care. Primary outcome assessment involves patient experience during chemotherapy using a standardized questionnaire. Secondary outcomes include evaluating severe chemotherapy-associated toxicity, assessing quality of life, and determining user satisfaction with the application. The research will adhere to intention-to-treat principles. This study has been registered at ClinicalTrials.gov (NCT06077123).</jats:p>
4Scopus© Citations 2
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Effects on Quality of Life of a Telemonitoring Platform amongst Patients with Cancer (EQUALITE): A Randomized Trial Protocol
(2024)
Felipe Martínez
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Carla Taramasco
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Manuel Espinoza
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ACEVEDO ROMO, JOHANNA PATRICIA
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Carolina Goic
<jats:p>Cancer, a pervasive global health challenge, necessitates chemotherapy or radiotherapy treatments for many prevalent forms. However, traditional follow-up approaches encounter limitations, exacerbated by the recent COVID-19 pandemic. Consequently, telemonitoring has emerged as a promising solution, although its clinical implementation lacks comprehensive evidence. This report depicts the methodology of a randomized trial which aims to investigate whether leveraging a smartphone app called Contigo for disease monitoring enhances self-reported quality of life among patients with various solid cancers compared to standard care. Secondary objectives encompass evaluating the app’s impact on depressive symptoms and assessing adherence to in-person appointments. Randomization will be performed independently using an allocation sequence that will be kept concealed from clinical investigators. Contigo offers two primary functions: monitoring cancer patients’ progress and providing educational content to assist patients in managing common clinical situations related to their disease. The study will assess outcomes such as quality of life changes and depressive symptom development using validated scales, and adherence to in-person appointments. Specific scales include the EuroQol Group’s EQ-5D questionnaire and the Patient Health Questionnaire (PHQ-9). We hypothesize that the use of Contigo will assist and empower patients receiving cancer treatment, which will translate to better quality of life scores and a reduced incidence of depressive symptoms. All analyses will be undertaken with the intention-to-treat principle by a statistician unaware of treatment allocation. This trial is registered in ClinicalTrials under the registration number NCT06086990.</jats:p>
Scopus© Citations 2 2
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Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
(2023)
Linda Zollner
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Felix Boekstegers
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Carol Barahona Ponce
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Dominique Scherer
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Katherine Marcelain
<jats:p>A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.</jats:p>
Scopus© Citations 13 1
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Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high‐incidence country
(2023)
Felix Boekstegers
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Dominique Scherer
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Carol Barahona Ponce
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Katherine Marcelain
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Valentina Gárate‐Calderón
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
5Scopus© Citations 16
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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)
Alice Blandino
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Dominique Scherer
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Trine B. Rounge
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Sinan U. Umu
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Felix Boekstegers
<jats:p>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 (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 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.</jats:p>
12Scopus© Citations 8

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