Browsing by Author "Cortes, Analia"

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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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    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.
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    Moderate hypofractionated radiotherapy to the prostate bed with or without pelvic lymph nodes: a prospective trial
    (2024) Canales, Juan P.; Barnafi, Esteban; Salazar, Cristian; Reyes, Paula; Merino, Tomas; Calderon, David; Cortes, Analia
    Background: Hypofractionated radiotherapy in the treatment of prostate cancer has been widely studied. However, in the postoperative setting it has been less explored. The objective of this prospective study is to evaluate the safety and efficacy of hypofractionated radiotherapy in postoperative prostate cancer. Materials and methods: A prospective study was designed to include patients with prostate cancer with an indication of postoperative radiotherapy as adjuvant or salvage. A hypofractionated radiotherapy scheme of 51 Gy in 17 fractions was performed with the possibility of treating the pelvis at a dose of 36 Gy in 12 fractions sequentially. Safety was evaluated based on acute and late toxicity [according to the Radiation Therapy Oncology Group (RTOG) scale and Common Terminology Criteria Adverse Events (CTCAE) v4.03], International Prognostic Scoring System (IPSS) over time, and quality of life. Results: From August 2020 to June 2022, 31 patients completed treatment and were included in this report. 35.5% of patients received elective treatment of the pelvic nodal areas. Most patients reported minimal or low acute toxicity, with an acute gastrointestinal (GI) and genitourinary (GU) grade 3 or greater toxicity of 3.2% and 0%, respectively. The evolution in time of the IPSS remained without significant differences (p = 0.42). With the exception of a significant improvement in the domains of hormonal and sexual symptoms of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, the rest of the domains [EPIC, European Organization for Research and Treatment of Cancer (EORTC) Core quality of life questionnaire (C-30) and Prostate Cancer module (PR-25)] were maintained without significant differences over time. With a follow-up of 15.4 months, late GI and GU grade 2 toxicity was reported greater than 0% and 9.6%, respectively. Conclusions: Hypofractionated radiotherapy in postoperative prostate cancer appears to be safe with low reports of relevant acute or late toxicity. Further follow-up is required to confirm these results. Trial registration: The protocol was approved by the accredited Medical Ethical Committee of Pontificia Universidad Cat & oacute;lica de Chile. All participants accepted and wrote informed consent.