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1. Prenatal inflammation remodels lung immunity and function by programming ILC2 hyperactivation

Author

Diego A. López, Aleah Griffin, Lorena Moreno Aguilar, Cassandra Deering-Rice, Elizabeth J. Myers, Kristi J. Warren, Robert S. Welner, and Anna E. Beaudin

Subjects
CP: Immunology, Biology (General), QH301-705.5
Abstract

Summary: Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation is recapitulated by adoptive transfer of fetal liver precursors following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, is concomitant with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a mechanism by which early-life inflammation results in increased asthma susceptibility in the presence of hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.

Published
2024
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2. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis

Author

Nikos Papadimitriou, Niki Dimou, Konstantinos K. Tsilidis, Barbara Banbury, Richard M. Martin, Sarah J. Lewis, Nabila Kazmi, Timothy M. Robinson, Demetrius Albanes, Krasimira Aleksandrova, Sonja I. Berndt, D. Timothy Bishop, Hermann Brenner, Daniel D. Buchanan, Bas Bueno-de-Mesquita, Peter T. Campbell, Sergi Castellví-Bel, Andrew T. Chan, Jenny Chang-Claude, Merete Ellingjord-Dale, Jane C. Figueiredo, Steven J. Gallinger, Graham G. Giles, Edward Giovannucci, Stephen B. Gruber, Andrea Gsur, Jochen Hampe, Heather Hampel, Sophia Harlid, Tabitha A. Harrison, Michael Hoffmeister, John L. Hopper, Li Hsu, José María Huerta, Jeroen R. Huyghe, Mark A. Jenkins, Temitope O. Keku, Tilman Kühn, Carlo La Vecchia, Loic Le Marchand, Christopher I. Li, Li Li, Annika Lindblom, Noralane M. Lindor, Brigid Lynch, Sanford D. Markowitz, Giovanna Masala, Anne M. May, Roger Milne, Evelyn Monninkhof, Lorena Moreno, Victor Moreno, Polly A. Newcomb, Kenneth Offit, Vittorio Perduca, Paul D. P. Pharoah, Elizabeth A. Platz, John D. Potter, Gad Rennert, Elio Riboli, Maria-Jose Sánchez, Stephanie L. Schmit, Robert E. Schoen, Gianluca Severi, Sabina Sieri, Martha L. Slattery, Mingyang Song, Catherine M. Tangen, Stephen N. Thibodeau, Ruth C. Travis, Antonia Trichopoulou, Cornelia M. Ulrich, Franzel J. B. van Duijnhoven, Bethany Van Guelpen, Pavel Vodicka, Emily White, Alicja Wolk, Michael O. Woods, Anna H. Wu, Ulrike Peters, Marc J. Gunter, and Neil Murphy

Subjects
Science
Abstract

Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.

Published
2020
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3. Strengthening the Link between Vaccine Predispositions and Vaccine Advocacy through Certainty

Author

Borja Paredes, Miguel A. Martín Cárdaba, Lorena Moreno, Nerea Cano, Pablo Briñol, Ubaldo Cuesta, and Richard E. Petty

Subjects
beliefs about medicines questionnaire (BMQ), vaccination attitudes examination scale (VAX), vaccination advocacy, individual differences, meta-cognition, certainty, Medicine
Abstract

Background. Instruments designed to assess individual differences in predispositions towards vaccination are useful in predicting vaccination-related outcomes. Despite their importance, there is relatively little evidence regarding the conditions under which these instruments are more predictive. The current research was designed to improve the ability of these kinds of instruments to predict vaccination advocacy by considering the certainty associated with the responses to vaccination scales. Method. Across two studies, participants completed the Beliefs about Medicines Questionnaire BMQ scale (Study 1) or the Vaccination Attitudes Examination (VAX) scale (Study 2). The certainty participants had in their responses to each scale was either measured (Study 1) or manipulated (Study 2). Intentions to advocate in favor of vaccination served as the criterion measure in both studies. Results. As expected, the scales significantly predicted vaccination advocacy, contributing to enhancing the predictive validity of the instruments used in the studies. Most relevant, certainty moderated the extent to which these scales predicted vaccination advocacy, with greater consistency between the initial scores and the subsequent advocacy willingness obtained for those with higher certainty. Conclusions. Certainty can be useful to predict when the relationship between vaccination-related cognitions (i.e., beliefs or attitudes) and advocacy willingness is likely to be stronger.

Published
2022
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4. Effect of Operating Conditions and Fructans Size Distribution on Tight Ultrafiltration Process for Agave Fructans Fractionation: Optimization and Modeling

Author

Noe Luiz-Santos, Rogelio Prado-Ramírez, Rosa María Camacho-Ruíz, Guadalupe María Guatemala-Morales, Enrique Arriola-Guevara, and Lorena Moreno-Vilet

Subjects
fractionation, fine ultrafiltration, agave fructans, modeling, Chemical technology, TP1-1185, Chemical engineering, TP155-156
Abstract

The objective of this work was to evaluate the effect of operating conditions and fructans size distribution on the tight Ultrafiltration process for agave fructans fractionation. A mathematical model of limiting mass flux transfer was used to represent the profile of concentrations over time at the outlet of a pilot scale ultrafiltration system. First, a Box-Behnken experimental design was performed for the optimization of the parameters that determine the operating conditions in their respective ranges: temperature, 30–60 °C; transmembrane pressure (TMP), 1–5 bar and feed concentration, 50–150 kg∙m−3, on the separation factor (SF) and permeate flux. Then, the validation of the model for different fructans size distribution was carried out. The results showed that for SF, the quadratic terms of temperature, TMP and feed concentration were the most significant factors. Statistical analysis revealed that the temperature-concentration interaction has a significant effect (p < 0.005) and that the optimal conditions were: 46.81 °C, 3.27 bar and 85.70 kg∙m−3. The optimized parameters were used to validate the hydrodynamic model; the adjustments conclude that the model, although simplified, is capable of correctly reproducing the experimental data of agave fructans fractionation by a tight ultrafiltration pilot unit. The fractionation process is favored at higher proportions of FOS:Fc in native agave fructans.

Published
2022
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6. Pharmacotherapy of Traumatic Childhood Aphasia: Beneficial Effects of Donepezil Alone and Combined With Intensive Naming Therapy

Author

Guadalupe Dávila, María Pilar Moyano, Lisa Edelkraut, Lorena Moreno-Campos, Marcelo L. Berthier, María José Torres-Prioris, and Diana López-Barroso

Subjects
language, childhood aphasia, anomia, traumatic brain injury, donepezil, pharmacological treatment, Therapeutics. Pharmacology, RM1-950
Abstract

At present, language therapy is the only available treatment for childhood aphasia (CA). Studying new interventions to augment and hasten the benefits provided by language therapy in children is strongly needed. CA frequently emerges as a consequence of traumatic brain injury and, as in the case of adults, it may be associated with dysfunctional activity of neurotransmitter systems. The use of cognitive-enhancing drugs, alone or combined with aphasia therapy, promotes improvement of language deficits in aphasic adults. In this study we report the case of a 9-year-old right-handed girl, subject P, who had chronic anomic aphasia associated with traumatic lesions in the left temporal-parietal cortex. We performed a single-subject, open-label study encompassing administration of the cholinergic agent donepezil (DP) alone during 12 weeks, followed by a combination of DP and intensive naming therapy (INT) for 2 weeks and thereafter by a continued treatment of DP alone during 12 weeks, a 4-week washout period, and another 2 weeks of INT. Four comprehensive language and neuropsychological evaluations were performed at different timepoints along the study, and multiple naming evaluations were performed after each INT in order to assess performance in treated and untreated words. Structural magnetic resonance imaging (MRI) was performed at baseline. MRI revealed two focal lesions in the left hemisphere, one large involving the posterior inferior and middle temporal gyri and another comprising the angular gyrus. Overall, baseline evaluation disclosed marked impairment in naming with mild-to-moderate compromise of spontaneous speech, repetition, and auditory comprehension. Executive and attention functions were also affected, but memory, visuoconstructive, and visuoperceptive functions were preserved. Treatment with DP alone significantly improved spontaneous speech, auditory comprehension, repetition, and picture naming, in addition to processing speed, selective, and sustained attention. Combined DP-INT further improved naming. After washout of both interventions, most of these beneficial changes remained. Importantly, DP produced no side effects and subject P attained the necessary level of language competence to return to regular schooling. In conclusion, the use of DP alone and in combination with INT improved language function and related cognitive posttraumatic deficits in a child with acquired aphasia. Further studies in larger samples are warranted.

Published
2020
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7. Developmental Dynamic Dysphasia: Are Bilateral Brain Abnormalities a Signature of Inefficient Neural Plasticity?

Author

Marcelo L. Berthier, Guadalupe Dávila, María José Torres-Prioris, Ignacio Moreno-Torres, Jordi Clarimón, Oriol Dols-Icardo, María J. Postigo, Victoria Fernández, Lisa Edelkraut, Lorena Moreno-Campos, Diana Molina-Sánchez, Paloma Solo de Zaldivar, and Diana López-Barroso

Subjects
dynamic aphasia, congenital mirror movements, developmental cerebral anomalies, neuroimaging, brain stimulation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language, and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement.

Published
2020
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8. Identification of Lynch Syndrome Carriers among Patients with Small Bowel Adenocarcinoma

Author

Ariadna Sánchez, Luis Bujanda, Miriam Cuatrecasas, Alex Bofill, Cristina Alvarez-Urturi, Goretti Hernandez, Lara Aguilera, Sabela Carballal, Joan Llach, Cristina Herrera-Pariente, Mar Iglesias, Liseth Rivero-Sánchez, Gerhard Jung, Lorena Moreno, Teresa Ocaña, Carolina Bayarri, Maria Pellise, Antoni Castells, Sergi Castellví-Bel, Francesc Balaguer, and Leticia Moreira

Subjects
Lynch syndrome, small bowel adenocarcinoma, hereditary cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families.

Published
2021
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9. Effect of Ultrasound-Assisted Extraction Parameters on Total Polyphenols and Its Antioxidant Activity from Mango Residues (Mangifera indica L. var. Manililla)

Author

Anahí J. Borrás-Enríquez, Elizabeth Reyes-Ventura, Socorro J. Villanueva-Rodríguez, and Lorena Moreno-Vilet

Subjects
mango, Manililla, waste, ultrasound, solvent, amplitude, Physics, QC1-999, Chemistry, QD1-999
Abstract

Manililla is a mango variety whose residues contain bioactive compounds such as polyphenols and flavonoids, with high added value. The use of environmentally friendly extraction technology would be of great relevance; hence, this study aimed to evaluate the effect of solvent relation, sonication time and amplitude on the ultrasound-assisted extraction of total polyphenols in Manililla mango residues (peel, endocarp and kernel) and antioxidant activity. An experimental design 23 with a central point was used to evaluate the curvature behavior of the process variables. Conventional maceration was used as a control. The better conditions were obtained at the central point using 50% ethanol in water, 60% amplitude and 20 min of sonication time. We obtained values of up to 1814 mg GAE/100 g, 469 mg GAE/100 g and 672 mg GAE/100 g of total polyphenols and 1228 mg QE/100 g, 653 mg QE/100 g and 880 mg QE/100 g of total flavonoids for peel, endocarp and kernel, respectively. Mangiferin was quantified in ultrasound-assisted extraction at 150 mg/g in peel and 0.025 mg/g in the kernel, but it was not detectable in maceration. An antioxidant capacity of 87%, 14% and 83% inhibition for peel, endocarp and kernel, respectively, were obtained. Peel and kernel were the residues with higher potential as extraction material, while endocarp was not.

Published
2021
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10. Situación funcional, autopercepción de salud y nivel de actividad física en pacientes con artrosis

Author

Carmen Llanos Val Jiménez, Jesús López-Torres Hidalgo, Eva María García Atienza, María Soledad Navarro Ruiz, Inmaculada Hernández Cerón, and Lorena Moreno de la Rosa

Subjects
Artrosis, WOMAC, Actividad física, Atención primaria, Medicine (General), R5-920
Abstract

Objetivo: Describir la situación funcional y la autopercepción de salud de los pacientes con osteoartritis (OA) en atención primaria, comprobando su relación con el nivel de actividad física y las características sociodemográficas. Diseño: Estudio de prevalencia y asociación cruzada. Emplazamiento: Consultas de medicina de familia. Participantes: Pacientes adultos diagnosticados en su historia clínica de OA de cualquier localización articular. De un total de 487, participaron 346 (71,0%). Mediciones principales: Capacidad funcional (escala WOMAC), nivel de autopercepción de salud (cuestionario EuroQoL-5D), nivel de actividad física (cuestionario IPAQ), número de articulaciones afectadas, nivel de dolor (EVA) y características sociodemográficas. Resultados: En la escala WOMAC se obtuvo una puntuación media de 30,2 (DE: 20,8; IC 95%: 28,0-32,4), correspondiendo a dolor, rigidez y capacidad funcional puntuaciones de 6,5 (DE: 4,8), 1,9 (DE: 2,0) y 21,7 (DE: 15,7), respectivamente. La puntuación presentó una tendencia lineal (p

Published
2017
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11. SATISFACCIÓN CON EL TRATAMIENTO EN PACIENTES DE ATENCIÓN PRIMARIA CON ARTROSIS

Author

Carmen Llanos Val Jiménez, Jesús López-Torres Hidalgo, Eva María García Atienza, María Soledad Navarro Ruiz, Inmaculada Hernández Cerón, and Lorena Moreno de la Rosa

Subjects
Medicine, Public aspects of medicine, RA1-1270
Abstract

Fundamentos: Al igual que en otros problemas crónicos, en el abor - daje del paciente con artrosis se tiende a un modelo de toma de decisiones compartidas, en el que el punto de vista del paciente debe ser considerado en la elección del tratamiento. El objetivo de este trabajo fue evaluar la sa - tisfacción con el tratamiento en pacientes diagnosticados de osteoartrosis y comprobar si existen diferencias entre diferentes opciones farmacológicas, así como determinar si existe asociación con el estado funcional y las carac - terísticas clínicas y sociodemográficas. Métodos: Se realizó un estudio observacional transversal en una muestra de 487 pacientes seleccionados mediante muestreo consecutivo. La variable principal fue el nivel de satisfacción con el tratamiento (cuestionario ARTS). El estado funcional de los pacientes fue evaluado mediante la escala WO - MAC. Otras variables fueron: características del tratamiento, adherencia te - rapéutica, eventos adversos, y variables clínicas y sociodemográficas. Resultados: En el cuestionario ARTS los pacientes, en un rango entre 28 y 87, obtuvieron una puntuación media de 65,3 (DE: 9,9). La puntuación no fue significativamente diferente en consumidores de 1, 2 o más fármacos. Entre quienes consumían un solo fármaco, no hubo diferencias entre los di - ferentes tipos de fármacos. En el estado funcional se obtuvo una puntuación media de 30,2 puntos (DE: 20,8) y se observó una débil correlación negativa con el nivel de satisfacción (r= - 0,252; p

Published
2017

12. Comparative data of molecular weight distribution of agave fructans fractions using MALDI-ToF and HPLC-SEC

Author

Lorena Moreno-Vilet, Stéphane Bostyn, José-Luis Flores-Montaño, and Rosa-María Camacho-Ruiz

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

A comparative data of two generally accepted mass techniques for estimate the molecular weight distribution of polysaccharides are presented. The data were obtained from agave fructans samples of different molecular weight, which were analyzed authored independently. The two analytical techniques used were Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-ToF) and High Pressure Size Exclusion Chromatography (HP-SEC). The data set here are related to the research paper entitled “Size-exclusion chromatography (HPLC-SEC) technique optimization by simplex method to estimate molecular weight distribution of agave fructans” by Moreno-Vilet et al. [1]. This article present the comparative figures as histograms obtained from mathematically processed MALDI-ToF spectra and HPLC-SEC chromatograms. And also, the calculated polymer parameters as number and mass molecular weight, number and mass average degree of polymerization and dispersity index.

Published
2019
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13. Germline and Somatic Whole-Exome Sequencing Identifies New Candidate Genes Involved in Familial Predisposition to Serrated Polyposis Syndrome

Author

Yasmin Soares de Lima, Coral Arnau-Collell, Marcos Díaz-Gay, Laia Bonjoch, Sebastià Franch-Expósito, Jenifer Muñoz, Leticia Moreira, Teresa Ocaña, Miriam Cuatrecasas, Cristina Herrera-Pariente, Sabela Carballal, Lorena Moreno, Aránzazu Díaz de Bustamante, Antoni Castells, Luis Bujanda, Joaquín Cubiella, Daniel Rodríguez-Alcalde, Francesc Balaguer, and Sergi Castellví-Bel

Subjects
serrated polyposis syndrome, genetic predisposition to disease, colorectal cancer, whole-exome sequencing, mutational signatures, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The serrated polyposis syndrome (SPS) is the most common and yet underdiagnosed colorectal polyposis syndrome. It is characterized by multiple and/or large colonic serrated polyps and a higher associated risk for colorectal cancer (CRC). The main objective of this study was to identify new candidate genes involved in the germline predisposition to SPS/CRC. Thirty-nine SPS patients from 16 families (≥2 patients per family) were recruited without alterations in well-known hereditary CRC genes, and germline and somatic whole-exome sequencing were performed. Germline rare variants with plausible pathogenicity, located in genes involved in cancer development, senescence and epigenetic regulation were selected. Somatic mutational profiling and signature analysis was pursued in one sample per family, when possible. After data filtering, ANXA10, ASXL1, CFTR, DOT1L, HIC1, INO80, KLF3, MCM3AP, MCM8, PDLIM2, POLD1, TP53BP1, WNK2 and WRN were highlighted as the more promising candidate genes for SPS germline predisposition with potentially pathogenic variants shared within families. Somatic analysis characterized mutational profiles in advanced serrated polyps/tumors, revealing a high proportion of hypermutated samples, with a prevalence of clock-like mutational signatures in most samples and the presence of DNA mismatch repair-defective signatures in some cases. In conclusion, we identified new candidate genes to be involved in familial SPS. Further functional studies and replication in additional cohorts are required to confirm the selected candidates.

Published
2021
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14. Performance Evaluation of Tight Ultrafiltration Membrane Systems at Pilot Scale for Agave Fructans Fractionation and Purification

Author

Noe Luiz-Santos, Rogelio Prado-Ramírez, Enrique Arriola-Guevara, Rosa-María Camacho-Ruiz, and Lorena Moreno-Vilet

Subjects
fine ultrafiltration, agave fructans, ceramic membrane, polymeric membrane, rejection coefficient, Chemical technology, TP1-1185, Chemical engineering, TP155-156
Abstract

Ceramic and polymeric membrane systems were compared at the pilot scale for separating agave fructans into different molecular weight fractions that help to diversify them into more specific industrial applications. The effect of the transmembrane pressure of ultrafiltration performance was evaluated through hydraulic permeability, permeate flux and rejection coefficients, using the same operating conditions such as temperature, feed concentration and the molecular weight cut-off (MWCO) of membranes. The fouling phenomenon and the global yield of the process were evaluated in concentration mode. A size distribution analysis of agave fructans is presented and grouped by molecular weight in different fractions. Great differences were found between both systems, since rejection coefficients of 68.6% and 100% for fructans with degrees of polymerization (DP) > 10, 36.3% and 99.3% for fructooligosaccharides (FOS) and 21.4% and 34.2% for mono-disaccharides were obtained for ceramic and polymeric membrane systems, respectively. Thus, ceramic membranes are better for use in the fractionation process since they reached a purity of 42.2% of FOS with a yield of 40.1% in the permeate and 78.23% for fructans with DP > 10 and a yield of 70% in the retentate. Polymeric membranes make for an efficient fructan purification process, eliminating only mono-disaccharides, and reaching a 97.7% purity (considering both fructan fractions) with a yield of 64.3% in the retentate.

Published
2020
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15. Genetic Counseling for Hereditary Gastric and Pancreatic Cancer in High-Risk Gastrointestinal Cancer Clinics: An Effective Strategy

Author

Joan Llach, Lorena Moreno, Ariadna Sánchez, Cristina Herrera-Pariente, Teresa Ocaña, Miriam Cuatrecasas, Liseth Rivero-Sánchez, Rebeca Moreira, Mireia Díaz, Gerhard Jung, Maria Pellisé, Antoni Castells, Francesc Balaguer, Sabela Carballal, and Leticia Moreira

Subjects
gastric cancer, pancreatic cancer, hereditary cancer, familial cancer, genetic counselling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The identification of high-risk groups of gastric (GC) and pancreatic adenocarcinoma (PC) due to a hereditary basis could imply a benefit in the affected families by establishing personalized preventive strategies. We aimed at assessing the diagnostic yield of GC/PC hereditary syndromes in individuals evaluated based on specific clinical criteria. In total, 77 unrelated individuals (45 from GC group/32 from PC group) were recruited: 51 (66.2%) cancer diagnosis ≤60 years, 3 (4%) with personal history of GC/PC and other cancer and 23 (29.8%) due to family history. Immunohistochemical analysis of DNA mismatch repair proteins was performed in 38 (49.3%) available tumors, being pathological in one (2%) GC. A genetic analysis was performed if clinical criteria of hereditary syndrome were fulfilled, identifying a mutation in 10/22 (45.5%) families [7/16 (43.7%) with GC and 3/6 (50%) with PC] and 19 (24.7%) fulfilled criteria of familial cancer. Diagnosis of cancer p = 0.007 and OR:17.4 (95% IC 2.5–119.9); p = 0.004; respectively]. The selection of patients based on clinical criteria leads to high diagnostic yield, detecting a causative germline mutation in almost half of the cases; therefore, both meticulous genetic counseling and use of multi-gen panels is crucial.

Published
2020
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16. Colorectal cancer after negative colonoscopy in fecal immunochemical test-positive participants from a colorectal cancer screening program

Author

Liseth Rivero-Sánchez, Jaume Grau, Josep María Augé, Lorena Moreno, Angels Pozo, Anna Serradesanferm, Mireia Díaz, Sabela Carballal, Ariadna Sánchez, Leticia Moreira, Francesc Balaguer, Maria Pellisé, and Antoni Castells

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and study aims Colorectal cancer (CRC) risk after a positive fecal immunochemical test (FIT) and negative colonoscopy is unknown. We aimed to ascertain the cumulative incidence of post-colonoscopy colorectal cancer (PCCRC) and the manifestation of other lesions that could explain the test positivity in individuals with a negative colonoscopy in a population screening program. Patients and method Observational study in participants from the first round of a CRC screening program (2010 – 2012) with positive-FIT (≥ 20 μg/g of feces) and negative colonoscopy (without neoplasia). A 42- to 76-month follow-up was performed searching in the National Health Service database and by a brief structured telephonic interview. Results Of 2659 FIT-positive individuals who underwent colonoscopy, 811 (30.5 %) had a negative colonoscopy. Three PCCRC (0.4 %) were detected within 11 – 28 months and accelerated carcinogenesis was ruled out. Among those with normal colonoscopy, 32 (5 %) relevant lesions were detected at follow-up. One-third of them (11/32) were significant neoplasias: a gastric cancer, a small-bowel lymphoma, six advanced colorectal adenomas, and the three PCCRC. The 21 remaining lesions were inflammatory, vascular disorders, or non-advanced colorectal adenomas. Conclusions The vast majority (95 %) of individuals did not present any subsequent lesion that could explain the FIT positivity. The very low incidence (0.4 %) and characteristics of PCCRC observed in our cohort reinforce the concept that, although a positive FIT preselects high risk individuals, a high quality colonoscopy is the paramount factor in preventing PCCRC. Improving quality standards of colonoscopy are required to strengthen the current CRC screening strategies.

Published
2018
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17. Investigar la Historia Contemporánea en España: a la sombra de la Ley de Secretos Oficiales

Author

Antonio Malalana Ureña and Lorena Moreno Pérez

Subjects
Acceso al documento, Restricción de acceso a la información, Archivos administrativos, Archivos estatales, Ley de Secretos Oficiales, History (General), D1-2009
Abstract

El acceso sin trabas a los archivos es condición básica para la investigación histórica y para garantizar la información y la transparencia en la gestión pública. Sin embargo, estos derechos no siempre están asegurados. Para los ciudadanos y los historiadores, el pleno acceso a los archivos es una cuestión pendiente en lo tocante a algunos documentos de la Historia Contemporánea española, lo que ha frustrado, además, la posibilidad de atender el derecho a la verdad, a la justicia y a la reparación que demanda el Derecho Internacional Humanitario para las víctimas de la Guerra Civil y del Franquismo.

Published
2017
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18. Analysis of A 6-Mirna Signature in Serum from Colorectal Cancer Screening Participants as Non-Invasive Biomarkers for Advanced Adenoma and Colorectal Cancer Detection

Author

María Marcuello, Saray Duran-Sanchon, Lorena Moreno, Juan José Lozano, Luis Bujanda, Antoni Castells, and Meritxell Gironella

Subjects
colorectal cancer, screening, non-invasive biomarker, early detection, advanced adenoma, circulating mirna, serum, liquid biopsy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.

Published
2019
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19. School-Based Obesity Prevention Intervention in Chilean Children: Effective in Controlling, but not Reducing Obesity

Author

Juliana Kain, Fernando Concha, Lorena Moreno, and Bárbara Leyton

Subjects
Internal medicine, RC31-1245
Abstract

Objective. To evaluate the effectiveness of a 12-month multicomponent obesity prevention intervention. Setting. 9 elementary schools in Santiago, Chile. Subjects. 6–8 y old low-income children (N=1474). Design. Randomized controlled study; 5 intervention/4 control schools. We trained teachers to deliver nutrition contents and improve the quality of PE classes. We determined % healthy snacks brought from home, children’s nutrition knowledge, nutritional status, duration of PE classes, and % time in moderate/vigorous activity (MVA). Effectiveness was determined by comparing Δ BMI Z between intervention and control children using PROCMIXED. Results. % obesity increased in boys from both types of schools and in girls from control schools, while decreasing in girls from intervention schools (all nonsignificant). % class time in MVA declined (24.5–16.2) while remaining unchanged (24.8–23.7%) in classes conducted by untrained and trained teachers, respectively. In boys, BMI Z declined (1.33–1.24) and increased (1.22–1.35) in intervention and control schools, respectively. In girls, BMI Z remained unchanged in intervention schools, while increasing significantly in control schools (0.91–1.06, P=0.024). Interaction group * time was significant for boys (P

Published
2014
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20. Study of Enzymatic Hydrolysis of Fructans from Agave salmiana Characterization and Kinetic Assessment

Author

Christian Michel-Cuello, Imelda Ortiz-Cerda, Lorena Moreno-Vilet, Alicia Grajales-Lagunes, Mario Moscosa-Santillán, Johanne Bonnin, Marco Martín González-Chávez, and Miguel Ruiz-Cabrera

Subjects
Technology, Medicine, Science
Abstract

Fructans were extracted from Agave salmiana juice, characterized and subjected to hydrolysis process using a commercial inulinase preparation acting freely. To compare the performance of the enzymatic preparation, a batch of experiments were also conducted with chicory inulin (reference). Hydrolysis was performed for 6 h at two temperatures (50, 60∘C) and two substrate concentrations (40, 60 mg/ml). Hydrolysis process was monitored by measuring the sugars released and residual substrate by HPLC. A mathematical model which describes the kinetics of substrate degradation as well as fructose production was proposed to analyze the hydrolysis assessment. It was found that kinetics were significantly influenced by temperature, substrate concentration, and type of substrate (P

Published
2012
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24. Mo1151 COLORECTAL ADENOMA PREVALENCE AND INCIDENCE IN LYNCH SYNDROME BY GENE

Author

Sanchez, Ariadna, primary, Castillo, Joaquin, additional, Roos, Victorine, additional, Navarro, Matilde, additional, Pineda, Marta, additional, Oliva, Berta Caballol, additional, Calle, Lorena Moreno, additional, Carballal, Sabela, additional, Rodriguez-Alonso, Lorena, additional, Cajal, Teresa Ramon Y, additional, Llort, Gemma, additional, Piñol, Virginia, additional, Lopez-Fernandez, Adrià, additional, Salces, Inmaculada, additional, Picó, Maria Dolores, additional, Rivas, Laura, additional, Bujanda, Luis, additional, Garzon-Benavides, Marta, additional, Pizarro, Angeles, additional, De Castro, Eva M., additional, Lopez-Arias, Maria Jesús, additional, Poves, Carmen F., additional, Garau, Catalina, additional, Rodríguez-Alcalde, Daniel, additional, Herraiz, Maite, additional, Alvarez, Cristina, additional, Rivas, Andres Dacal, additional, Carrillo-Palau, Marta, additional, Cid, Lucía, additional, Ponce, Marta, additional, Barreiro-Alonso, Eva, additional, Saperas, Esteban, additional, Aguirre, Elena, additional, Ocaña, Teresa, additional, Rivero, Liseth, additional, Bessa, Xavier, additional, Cubiella, Joaquin, additional, Jover, Rodrigo, additional, Rodriguez-Moranta, Francisco, additional, Balmaña, Judit, additional, Brunet, Joan, additional, Castells, Antoni, additional, Dekker, Evelien, additional, Capella, Gabriel, additional, Moreira, Leticia, additional, Pellise, Maria, additional, and Balaguer, Francesc, additional

Published
2023
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25. Germline mutations inWNK2could be associated with serrated polyposis syndrome

Author

Yasmin Soares de Lima, Coral Arnau-Collell, Jenifer Muñoz, Cristina Herrera-Pariente, Leticia Moreira, Teresa Ocaña, Marcos Díaz-Gay, Sebastià Franch-Expósito, Miriam Cuatrecasas, Sabela Carballal, Anael Lopez-Novo, Lorena Moreno, Guerau Fernàndez, Aranzazu Díaz de Bustamante, Sophia Peters, Anna K Sommer, Isabel Spier, Iris B A W te Paske, Yasmijn J van Herwaarden, Antoni Castells, Luis Bujanda, Gabriel Capellà, Verena Steinke-Lange, Khalid Mahmood, JiHoon Eric Joo, Julie Arnold, Susan Parry, Finlay A Macrae, Ingrid M Winship, Christophe Rosty, Joaquin Cubiella, Daniel Rodríguez-Alcalde, Elke Holinski-Feder, Richarda de Voer, Daniel D Buchanan, Stefan Aretz, Clara Ruiz-Ponte, Laura Valle, Francesc Balaguer, Laia Bonjoch, and Sergi Castellvi-Bel

Subjects
All institutes and research themes of the Radboud University Medical Center, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Genetics, Genetics (clinical)
Abstract

BackgroundPatients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.MethodsAfter a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. TheWNK2gene was disrupted in HT-29 cells by gene editing, andWNK2variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion.ResultsWe identified 2 rare germline variants in theWNK2gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2.ConclusionAfter whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in theWNK2gene. Functional studies suggested germlineWNK2variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.

Published
2022

26. Maximal Sensitivity to Child Maltreatment at the Ages of 6 and 11 Years is Associated with the Risk of Bipolar Disorder

Author

Irene Montoro, Lorena Moreno, Patricia Mulet, Carlota Miró, Ainhoa Leunda, Martí Llaurador-Coll, Gerard Muntané, Martin H. Teicher, Elisabet Vilella, and Alfonso Gutiérrez-Zotes

Subjects
Clinical Psychology, Applied Psychology
Abstract

Adverse childhood experiences, including child maltreatment (CM), are relevant environmental risk factors for bipolar disorder (BD). However, little is known about the interaction of the type, duration and frequency of abuse with the timing of abuse in BD. The aim of this study was to investigate the different patterns of childhood trauma (frequency, type and chronology) between BD patients and healthy controls (HCs) and to identify BD-sensitive periods of exposure to CM that could influence functioning outcomes. The Maltreatment and Abuse Chronology Exposure (MACE) scale was used to evaluate the importance of the type and timing of maltreatment in a sample of 60 patients diagnosed with euthymic BD. Additionally, 76 HCs were recruited for comparison. All participants were of European-Caucasian origin and were assessed in the 2016-2019 period. To identify the variables that maximally differentiated the type and timing of exposure to CM between the BD and HC groups, a linear mixed effects model and random forest (RF) analyses were applied. We showed that multiplicity and severity, nonverbal emotional abuse, witnessing interparental violence and emotional neglect were the main factors associated with BD. In addition, regarding the occurrence of maltreatment in BD patients, we identified two sensitive periods with a principal peak at the age of 6 and a secondary peak at the age of 11. Functionality at the assessment time was associated with CM in adolescence for both HC and BD participants. Although the sample size and retrospective nature of the MACE instrument were the main limitations of our study, we were unable to explore the role of variables such as sex or socioeconomic status. We concluded that the multiplicity and sensitivity of CM exposure, mainly of the emotional type, during middle childhood are important risk factors for BD, at least in the European-Caucasian cultural setting.

Published
2022

27. Massive cardiomegaly

Author

Luisa María Charco-Roca, María Garví-López, and Lorena Moreno-De la Rosa

Subjects
General Medicine
Published
2023

29. Self-Validation Theory: Confidence can Increase but also Decrease Performance in Applied Settings

Author

Pablo Briñol, Richard E. Petty, Lorena Moreno, and Beatriz Gandarillas

Subjects
Linguistics and Language, General Psychology, Language and Linguistics
Abstract

This article presents self-validation theory (SVT) as a framework predicting when mental contents guide performance. First, we illustrate how confidence can validate people’s thoughts (goals, beliefs, identity) increasing and decreasing performance, depending on what thoughts are validated. This first section reviews examples of validation processes in guiding intellectual performance in academic settings, sport performance in athletes, as well as performance on diverse social tasks. SVT specifies moderating conditions for validation processes to operate. Therefore, in the second section of this review, we identify unique and testable moderators for metacognitive processes demonstrating when and for whom validation processes are more likely to occur. A third section calls for future research identifying new validating variables (e.g., preparation, courage) capable of increasing usage of unexplored thoughts relevant to performance (e.g., expectations). This final section examines new domains for validation (e.g., group performance, cheating in performance), discusses to what extent people can use self-validation strategies deliberatively to improve their performance and addresses when performance can be impaired by invalidation (e.g., due to identity threat).

Published
2023

30. Germline mutations in

Author

Yasmin, Soares de Lima, Coral, Arnau-Collell, Jenifer, Muñoz, Cristina, Herrera-Pariente, Leticia, Moreira, Teresa, Ocaña, Marcos, Díaz-Gay, Sebastià, Franch-Expósito, Miriam, Cuatrecasas, Sabela, Carballal, Anael, Lopez-Novo, Lorena, Moreno, Guerau, Fernàndez, Aranzazu, Díaz de Bustamante, Sophia, Peters, Anna K, Sommer, Isabel, Spier, Iris B A W, Te Paske, Yasmijn J, van Herwaarden, Antoni, Castells, Luis, Bujanda, Gabriel, Capellà, Verena, Steinke-Lange, Khalid, Mahmood, JiHoon Eric, Joo, Julie, Arnold, Susan, Parry, Finlay A, Macrae, Ingrid M, Winship, Christophe, Rosty, Joaquin, Cubiella, Daniel, Rodríguez-Alcalde, Elke, Holinski-Feder, Richarda, de Voer, Daniel D, Buchanan, Stefan, Aretz, Clara, Ruiz-Ponte, Laura, Valle, Francesc, Balaguer, Laia, Bonjoch, and Sergi, Castellvi-Bel

Abstract

Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.After a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. TheWe identified 2 rare germline variants in theAfter whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the

Published
2022

31. Ultrasonido a la cabecera del paciente: una herramienta diagnóstica en síndrome aórtico agudo en la Unidad de Cuidado Intensivo, reporte de caso

Author

Darío Isaías Pinilla Rojas, Andrés Felipe Yepes, Lorena Moreno Araque, David Rene Rodriguez Lima, and Mario Andrés Mercado Díaz

Subjects
03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Materials Science (miscellaneous), 030208 emergency & critical care medicine
Abstract

Resumen La diseccion aortica es una patologia potencialmente fatal y su mortalidad aumenta de 1% a 2% por cada hora en el retraso diagnostico durante las primeras 48 horas. La mayoria de los pacientes consultan por dolor toracico, sin embargo, aproximadamente el 30% tienen alguna presentacion atipica. Se presenta el caso de un paciente de 78 anos que ingresa por alteracion del estado de conciencia secundario a diseccion aortica con compromiso de los vasos del cuello. El diagnostico se realiza basado en ultrasonido a la cabecera del paciente realizando doppler transcraneal, ecografia cardiaca y abdominal focalizada.

Published
2021

32. 163 - ¿ES NECESARIO EL CRIBADO DE CÁNCER GÁSTRICO EN EL SÍNDROME DE LYNCH?

Author

Ariadna Sánchez, Andres Arango, Maria José Moreta, Joan Llach, Mireia Diaz Centeno, Adrià López Fernández, Inmaculada Salces, Gemma Llort, Luis Bujanda Fernández de Piérola, Marta Carrillo-Palau, Goretti Hernández Mesa, Daniel Rodríguez-Alcalde, Maria Dolores Pico Sala, Rodrigo Jover, Carmen Poves, Eva Barreiro-Alonso, Andres Dacal Rivas, Maite Herraiz Bayod, Joaquin Cubiella, Virginia Piñol, Beatriz Peñas, Lorena Moreno, Liseth Rivero Sánchez, Teresa Ocaña, Sabela Carballal, Antoni Castells, María Pellisé Urquiza, Francesc Balaguer, and Leticia Moreira Ruiz

Subjects
Hepatology, Gastroenterology
Published
2023

34. Abstract P6-01-09: Efficacy of platinum-based chemotherapy and germline mutational status in early-stage triple-negative breast cancer: a unicenter retrospective analysis with long-term follow-up

Author

Adela Rodríguez Hernández, Benedetta Conte, Laia Fernández, Fara Brasó-Maristany, Belén Pastor, Miriam Potrony, Lorena Moreno, Elia Grau, Joan Antón Puig-Butillé, Aurora Sánchez, Blanca González-Farré, Esther Sanfeliu, Olga Martínez-Sáez, Claudette Falato, Maria Vidal, Nuria Chic, Tomás Pascual, Francesco Schettini, Montserrat Muñoz, Francesc Balaguer, Aleix Prat, and Barbara Adamo

Subjects
Cancer Research, Oncology
Abstract

BACKGROUND: In early-stage triple negative breast cancer (TNBC), the addition of carboplatin (CBDCA) to neoadjuvant chemotherapy (CT) increases pathologic complete response (pCR) and relapsed-free survival. However, it is unclear whether CBDCA improves overall survival (OS). In addition, the prognostic and/or predictive role of pathogenic germline variants (PGV) in BRCA1/2 genes and other cancer risk in this setting is not fully understood. Here, we assessed the efficacy of (neo)adjuvant CBDCA and the prognostic and predictive role of a panel of 14 genes in patients (pts) with eTNBC. METHODS: This is a retrospective study on 117 pts diagnosed with early-stage TNBC between 2000-2021 at Hospital Clinic of Barcelona. Eighty-one pts (69%) were candidates for PGV testing. Overall, 14 genes (PGV) (BRCA1, BRCA2, PALB2, BRIP1, CHEK2, TP53, ATM, RAD51C, RAD51D, BARD1, MLH1, MSH2, MSH6 and PMS2) were assessed using the TruSight hereditary cancer panel (Illumina MySeq platform) according to local guidelines. Univariable and multivariable logistic regression and Cox regression analyses were performed to identify clinical and molecular predictors of pCR and relapse-free survival (RFS), respectively. Chi-squared or Fisher’s exact tests were used to assess characteristics’ distribution as appropriate. RESULTS: Of 117 pts, 83 (71%) received CT in the neoadjuvant setting and 28 (24%) in the adjuvant setting. CBDCA was added to standard CT in 68 pts (82%) in the neoadjuvant cohort and 7 pts (6%) in the adjuvant cohort. Among pts with germline testing, 32/81 (39%) harbored PGV. BRCA1 was the most frequently mutated gene (18/32, 56%), followed by BRCA2 (5/32, 16%), PALB2 (4/32, 13%), BRIP1 (2/32, 6%), CHEK2, TP53 and PMS2 (3/32, 6%). Percentages of pts receiving CBDCA were similar between patients with and without PGV (14/16,87% and wild type (53/67,79%)(p=0.120). In the neoadjuvant cohort (n=83), CBDCA was the only variable significantly associated with pCR at both univariate (pCR rates of 58.5% with CBCDA and 14.3% without CBCDA; odds ratio [OR]=8.2 [95% CIs 2.0-55.7], p=0.008) and remained statistically significant after adjusting for PGV, tumor size and nodal status (OR=6.9 [95% CIs 1.4-53.0], p=0.028). pCR rates according to PGV are reported in Table 1. In terms of RFS, addition of CBDCA to neoadjuvant therapy (hazard ratio [HR]=0.2 [0.1-0.45], p< 0.001), PGV (HR=0.2 [0.05-0.9], p=0.048), pCR (HR=0.2 [0.1-0.6], p=0.004) and nodal status (HR=5.1 [1.7-15.2], p< 0.003) were significantly associated with RFS in univariate analyses. In a multivariable model, CBDCA remained an independent predictor of improved RFS along with pCR. When the neoadjuvant and adjuvant cohort were pooled together (n=117), platinum-based CT remained significantly associated with better RFS (HR=0.2 [0.14-0.86], p=0.021) regardless of time of administration (i.e., neoadjuvant or adjuvant). With a median follow-up of 5 years, CBCDA use was not found associated with OS (HR=0.7 [0.3-1.8], p= 0.560). CONCLUSIONS: The addition of CBDCA to standard CT was significantly associated with pCR and RFS but not OS, consistent with the phase III data. The benefit in terms of RFS was independent of the presence and the type of pathogenic germline alterations. Table 1. pCR rates according to PGV Citation Format: Adela Rodríguez Hernández, Benedetta Conte, Laia Fernández, Fara Brasó-Maristany, Belén Pastor, Miriam Potrony, Lorena Moreno, Elia Grau, Joan Antón Puig-Butillé, Aurora Sánchez, Blanca González-Farré, Esther Sanfeliu, Olga Martínez-Sáez, Claudette Falato, Maria Vidal, Nuria Chic, Tomás Pascual, Francesco Schettini, Montserrat Muñoz, Francesc Balaguer, Aleix Prat, Barbara Adamo. Efficacy of platinum-based chemotherapy and germline mutational status in early-stage triple-negative breast cancer: a unicenter retrospective analysis with long-term follow-up [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-09.

Published
2023

35. INCIDENCIA, TASA DE DETECCIÓN DE ADENOMAS Y FACTORES DE RIESGO DE CRC SEGÚN EL GEN AFECTO EN EL SÍNDROME DE LYNCH

Author

Ariadna Sánchez, Joaquin Castillo, Victorine H. Roos, Núria Dueñas, Marta Pineda, Berta Caballol, Lorena Moreno, Sabela Carballal, Lorena Rodríguez-Alonso, Teresa Ramón y Cajal, Gemma Llort, Virginia Piñol, Adrià López Fernández, Inmaculada Salces, Maria Dolores Picó, Laura Rivas, Luis Bujanda, Marta Garzón, Angeles Pizarro, Eva Martínez de Castro, Maria Jesus López-Arias, Carmen Poves, Catalina Garau, Daniel Rodríguez- Alcalde, Maite Herraiz, Cristina Alvarez-Urrutia, Andrés Dacal, Marta Carrillo-Palau, Lucia Cid, Marta Ponce, Eva Barreiro-Alonso, Esteban Saperas, Elena Aguirre, Teresa Ocaña, Liseth Rivero- Sánchez, Xavier Bessa, Joaquin Cubiella, Rodrigo Jover, Francisco Rodríguez-Moranta, Judith Balmaña, Joan Brunet, Antoni Castells, Evelien Dekker, Gabriel Capella, Leticia Moreira, Maria Pellise, and Francesc Balaguer

Subjects
Hepatology, Gastroenterology
Published
2023

38. Integrating water-quality analysis in national household surveys: water and sanitation sector learnings of Ecuador

Author

Juan Carlos Palacios, Koenraad Vancraeynest, Mónica Pozo, Lorena Moreno, Fausto Jácome, and Robert E. S. Bain

Subjects
Sustainable development, lcsh:TD201-500, Sanitation, business.industry, 0208 environmental biotechnology, Context (language use), 02 engineering and technology, Water industry, 010501 environmental sciences, Management, Monitoring, Policy and Law, 01 natural sciences, Pollution, 020801 environmental engineering, lcsh:Water supply for domestic and industrial purposes, Development studies, Sustainability, Open defecation, Water quality, business, Waste Management and Disposal, Environmental planning, 0105 earth and related environmental sciences, Water Science and Technology
Abstract

To respond to the global Sustainable Development Goals framework, Ecuador through the National Institute of Statistics and Censuses (INEC) has been strengthening its monitoring system since 2016, specifically on SDG 6.1 and 6.2. The World Bank Group, UNICEF Ecuador Country Office and WHO/UNICEF Joint Monitoring Programme provided initial support. Additional parameters were included in household surveys, including a water sample analysis to detect presence or absence of E. coli bacteria, and the SDG indicators were adapted to the national context. Ecuador collected water-quality data in two national household surveys in 2016 and 2019, including water quality at household's point of consumption for the 2019 survey. This opens opportunities to extend the analysis beyond access to safely managed drinking water services, toward comparison of water quality between source and point of consumption, and analyzing correlations with other parameters, such as handwashing with soap, water treatment, and safe storage and open defecation. This article describes the principal findings of the extended analysis carried out by INEC, as well as the opportunities to present the results for sector advocacy and decision-making purposes. This study concludes that alignment of the national monitoring systems to the SDG 6.1 framework provided strong evidence that water quality is the principal bottleneck in the water sector in Ecuador. Water-quality testing at the point of consumption was evidenced, as well as the importance of household water treatment and possible effects of other hygiene practices like handwashing with soap and open defecation on water quality at the point of consumption.

Published
2020

39. Enfoque y manejo clínico de pacientes con enfermedad por SARS COV2 (Covid -19) en unidad de cuidado intensivo

Author

Yuliet Catherin Montaño Villalobos, Lorena Moreno Araque, José Antonio Rojas Gambasica, Eleine Ahumada Bayuelo, Fabio Romo Escorcia, Yamil Elias Jaller Bornacelli, Carlos Arturo Álvarez, Gonzalo Andrés Chavarro Falla, Nancy Carolina Ávila Arenas, and Juan David Urriago

Subjects
03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, 030212 general & internal medicine, General Medicine
Abstract

Esta es una revisión temática sobre aspectos relacionados con enfermedad por SARS COV2 (COVID-19) y la Unidad de Cuidados Intensivos. Se establecen algunos lineamientos para tener en cuenta ante la eventual necesidad de hospitalizar en la Unidad de Cuidados Intensivos a pacientes con COVID-19 críticamente enfermos, con intervención de la vía aérea, el uso de la ventilación mecánica y todas las condiciones tanto de seguridad, como clínicas y epidemiológicas que se generan en estas circunstancias. En Colombia aparece el primer caso de COVID-19 el 6 de marzo de 2020, como caso importado de una joven proveniente de Milán (Italia); a partir de ahí, cada día ha habido reporte de casos, todos con índice epidemiológico y noción de contagio de un paciente o persona infectada fuera del país, siendo para el 15 de marzo en horas de la mañana 34 casos, y crecimiento muy rápido. Para el 17 de marzo, dos días después, son 64 casos según boletín del Ministerio de Salud y Protección Social del país. Se considera que estamos en la fase de contención para pronto pasar a la mitigación con circulación interna del virus.

Published
2020

40. Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome

Author

Daniel Rodríguez-Alcalde, Angeles Pizarro, Maria Pellise, Cristina Romero, Berta Caballol, Lorena Moreno, Esteban Saperas, Eva Martinez de Castro, Gemma Llort, Laura Rivas, Catalina Garau, Ariadna Sánchez, Elena Aguirre, Sabela Carballal, Virginia Piñol, Eva Barreiro-Alonso, Matilde Navarro, Lorena Rodríguez-Alonso, Marta Garzon, Xavier Bessa, Teresa Ocaña, Marta Ponce, Carmen Poves, Inmaculada Salces, Gerhard Jung, Cristina Alvarez-Urrutia, Maite Herraiz, Liseth Rivero-Sánchez, Evelien Dekker, Joan Brunet, Judith Balmaña, Maribel Gonzalez-Acosta, Francesc Balaguer, Blai Morales-Romero, Luis Bujanda, Leticia Moreira, Joaquín Cubiella, Teresa Ramón y Cajal, Marta Pineda, Miquel Serra-Burriel, Victorine H. Roos, María Dolores Picó, Andres Dacal, Antoni Castells, Lucía Cid, Maria Jesus López-Arias, Rodrigo Jover, Francisco Rodríguez-Moranta, Gabriel Capellá, Marta Carrillo-Palau, Barbara A. J. Bastiaansen, Adrià López-Fernández, Gastroenterology and Hepatology, Graduate School, APH - Methodology, APH - Personalized Medicine, CCA - Imaging and biomarkers, CCA - Cancer Treatment and Quality of Life, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Adenoma, medicine.medical_specialty, Colorectal cancer, Colonoscopy, HNPCC, Chromoendoscopy, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Internal medicine, medicine, Humans, Cumulative incidence, Colonoscopy Quality, Colorectal Neoplasms, HNPCC, Hereditary Non-Polyposis Colorectal Cancer, Lynch syndrome, colonoscopy quality, colonoscopy, hereditary colorectal cancer, neoplasms, Early Detection of Cancer, Hereditary Colorectal Cancer, Hepatology, medicine.diagnostic_test, business.industry, Incidence, Incidence (epidemiology), Gastroenterology, Hereditary Nonpolyposis Colorectal Cancer, Odds ratio, colonoscopy quality, colonoscopy, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, digestive system diseases, Hereditary Non-Polyposis Colorectal Cancer, 030220 oncology & carcinogenesis, Lynch Syndrome, 030211 gastroenterology & hepatology, business, Colorectal Neoplasms
Abstract

BACKGROUND & AIMS: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability. We aimed to evaluate the impact of key colonoscopy quality indicators on adenoma detection and prevention of PCCRC in LS. METHODS: We conducted a multicenter study focused on LS carriers without previous CRC undergoing colonoscopy surveillance (n = 893). Incident colorectal neoplasia during surveillance and quality indicators of all colonoscopies were analyzed. We performed an emulated target trial comparing the results from the first and second surveillance colonoscopies to assess the effect of colonoscopy quality indicators on adenoma detection and PCCRC incidence. Risk analyses were conducted using a multivariable logistic regression model. RESULTS: The 10-year cumulative incidence of adenoma and PCCRC was 60.6% (95% CI, 55.5%-65.2%) and 7.9% (95% CI, 5.2%-10.6%), respectively. Adequate bowel preparation (odds ratio [OR], 2.07; 95% CI, 1.06-4.3), complete colonoscopies (20% vs 0%; P = .01), and panchromoendoscopy use (OR, 2.14; 95% CI, 1.15-3.95) were associated with significant improvement in adenoma detection. PCCRC risk was significantly lower when colonoscopies were performed during a time interval of less than every 3 years (OR, 0.35; 95% CI, 0.14-0.97). We observed a consistent but not significant reduction in PCCRC risk for a previous complete examination (OR, 0.16; 95% CI, 0.03-1.28), adequate bowel preparation (OR, 0.64; 95% CI, 0.17-3.24), or previous use of high-definition colonoscopy (OR, 0.37; 95% CI, 0.02-2.33). CONCLUSIONS: Complete colonoscopies with adequate bowel preparation and chromoendoscopy use are associated with improved adenoma detection, while surveillance intervals of less than 3 years are associated with a reduction of PCCRC incidence. In LS, high-quality colonoscopy surveillance is of utmost importance for CRC prevention.

Published
2022

41. Epigenome-Wide DNA Methylation Profiling of Normal Mucosa Reveals HLA-F Hypermethylation as a Biomarker Candidate for Serrated Polyposis Syndrome

Author

Gerhard Jung, Eva Hernández-Illán, Juan J. Lozano, Julia Sidorova, Jenifer Muñoz, Yasuyuki Okada, Enrique Quintero, Goretti Hernandez, Rodrigo Jover, Sabela Carballal, Miriam Cuatrecasas, Lorena Moreno, Mireia Diaz, Teresa Ocaña, Ariadna Sánchez, Liseth Rivero, Oswaldo Ortiz, Joan Llach, Antoni Castells, Maria Pellisé, Ajay Goel, Eduard Batlle, and Francesc Balaguer

Subjects
Epigenome, Mucous Membrane, Adenomatous Polyposis Coli, Argonaute Proteins, Histocompatibility Antigens Class I, Humans, Molecular Medicine, Regular Article, DNA Methylation, Colorectal Neoplasms, Biomarkers, Pathology and Forensic Medicine
Abstract

Serrated polyposis syndrome (SPS) is associated with a high risk for colorectal cancer. Intense promoter hypermethylation is a frequent molecular finding in the serrated pathway and may be present in normal mucosa, predisposing to the formation of serrated lesions. To identify novel biomarkers for SPS, fresh-frozen samples of normal mucosa from 50 patients with SPS and 19 healthy individuals were analyzed by using the 850K BeadChip Technology (Infinium). Aberrant methylation levels were correlated with gene expression using a next-generation transcriptome profiling tool. Two validation steps were performed on independent cohorts: first, on formalin-fixed, paraffin-embedded tissue of the normal mucosa; and second, on 24 serrated lesions. The most frequently hypermethylated genes were HLA-F, SLFN12, HLA-DMA, and RARRES3; and the most frequently hypomethylated genes were PIWIL1 and ANK3 ( ß = 10%; P 20%; r > 0.55; P

Published
2022

42. The Role of Meta-Cognitive Certainty on Pornography Consumption

Author

Borja, Paredes, Luz, Martínez, Ubaldo, Cuesta, Pablo, Briñol, Richard, Petty, and Lorena, Moreno

Subjects
Erotica, Humans, Self Report, Metacognition
Abstract

The Problematic Pornography Use Scale (PPUS) was originally designed to help predicting pornography consumption. Despite the frequency with which this scale is used in the scientific literature, there is still relatively little evidence regarding the predictive validity of this important instrument. This current research introduces a construct capable of improving the ability of the scale to predict pornography consumption (meta-cognitive certainty).Over two studies, participants completed the PPUS and the meta-cognitive certainty in their responses to the scale was measured (Study 1) or manipulated (Study 2). Self-reported porn consumption was the criterion measure in both studies, with an additional actual overt behavior relevant to consumption of porn included in Study 2.As expected, the PPUS significantly predicted porn consumption, confirming the predictive validity of the scale. More importantly, meta-cognitive certainty was capable of moderating the extent to which scores on the PPUS could predict porn consumption, with greater consistency between the PPUS and reported behavior from those with high (vs. low) meta-cognitive certainty.These data suggest that considering meta-cognitive certainty may be useful for predicting when the link between the PPUS and porn consumption is stronger.

Published
2021

43. Endocuff-assisted colonoscopy for surveillance of serrated polyposis syndrome: a multicenter randomized controlled trial

Author

Ariadna Sánchez, Coral Arnau-Collell, Cristina Rodríguez de Miguel, Josep Llach, Jorge López Vicente, Ignasi Puig, Mireia Díaz, Oswaldo Ortiz, Leticia Moreira, Liseth Rivero-Sánchez, Francesc Balaguer, Luis Hernandez Villalba, Sabela Carballal, Teresa Ocaña, Miriam Cuatrecasas, Lorena Moreno, and Maria Pellise

Subjects
Male, medicine.medical_specialty, Adenoma, Colorectal cancer, Population, Colonoscopy, Withdrawal time, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, education, Early Detection of Cancer, education.field_of_study, medicine.diagnostic_test, business.industry, Reproducibility of Results, Equipment Design, Middle Aged, medicine.disease, Serrated polyposis, Confidence interval, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, 030211 gastroenterology & hepatology, business
Abstract

Background and study aims Serrated polyposis syndrome (SPS) is a condition with high risk for colorectal cancer. The Endocuff device has been shown to increase adenoma detection in the general and screening population. We aimed to ascertain whether Endocuff-assisted colonoscopy increases detection of serrated lesions in comparison with standard colonoscopy during the surveillance of patients with SPS. Methods In a multicenter randomized controlled study, patients who met SPS criteria I and/or III under surveillance (previous resection of all serrated lesions ≥ 4 mm) were consecutively randomly allocated 1:1 to Endocuff-assisted colonoscopy or standard colonoscopy, performed by expert endoscopists. The main outcome was the mean number of serrated lesions detected per patient. Results 122 patients (standard colonoscopy n = 60; Endocuff-assisted colonoscopy n = 62; 59 % men; mean age 60.6 (standard deviation [SD] 7.5) were included at 4 centers. Baseline variables (demographic data, SPS phenotype, colorectal cancer [CRC] history, cumulative polyps, and follow-up), cecal intubation rate, and withdrawal time were similar between groups. There was no statistically significant difference between Endocuff-assisted colonoscopy and standard colonoscopy for the mean number of serrated lesions detected per patient: 5.8 (95 % confidence interval [95 %CI] 4.4 – 7.2) and 5.0 (3.9 – 6.1), respectively (P = 0.36). There were also no differences between Endocuff-assisted and standard colonoscopy for detection of sessile serrated lesions (mean number per patient 2.5 [1.3 – 3.6] vs. 2.0 [1.1 – 3.0], P = 0.54) and adenomas (0.9 [0.5 – 1.3] vs. 0.5 [0.3 – 0.7], P = 0.12). Conclusion Use of Endocuff-assisted colonoscopy did not significantly increase the number of serrated lesion detected per patient during surveillance of SPS.

Published
2019

44. Discovery of common and rare genetic risk variants for colorectal cancer

Author

Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository

Subjects
Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.

Published
2018

45. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author

Stephanie J. Weinstein, Rami Nassir, Fredrick R. Schumacher, Neil Murphy, M. Henar Alonso, Satu Männistö, Hedy S. Rennert, Manish Gala, Phyllis J. Goodman, Albert de la Chapelle, Tilman Kühn, Fränzel J.B. Van Duijnhoven, Paul D.P. Pharoah, Anshul Kundaje, Juergen Boehm, W. James Gauderman, Mark A. Jenkins, Vittorio Perduca, Polly A. Newcomb, Amanda I. Phipps, Christopher I. Li, Douglas F. Easton, Antonia Trichopoulou, Kristin E. Anderson, Daniel D. Buchanan, Peter C. Scacheri, William M. Grady, Liher Imaz, Veronika Vymetalkova, Wan-Ling Hsu, Prudence R. Carr, Martha L. Slattery, Keith R. Curtis, Elizabeth A. Platz, Sai Chen, Graham G. Giles, D. Timothy Bishop, David M. Levine, Michael Hoffmeister, Duncan C. Thomas, Roger L. Milne, Michael O. Woods, Michael C. Bassik, Andrea Gsur, Dallas R. English, David V. Conti, Sébastien Küry, Wolfgang Lieb, Jochen Hampe, Coral Arnau-Collell, Steven Gallinger, Emily White, John S. Grove, Antoni Castells, Hermann Brenner, Amanda E. Toland, Noralane M. Lindor, Aurora Perez-Cornago, David Duggan, Temitope O. Keku, Edith J. M. Feskens, Heather Hampel, Korbinian Weigl, Li Li, Li Hsu, Conghui Qu, Peter T. Campbell, John L. Hopper, Volker Arndt, Jenny Chang-Claude, Lorena Moreno, John A. Baron, Stephen N. Thibodeau, Robert E. Schoen, Jeroen R. Huyghe, Rachel Pearlman, Sanford D. Markowitz, Amanda J. Cross, Stephan Buch, Barbara L. Banbury, Thomas J. Hudson, Yu Ru Su, Marc J. Gunter, Stephen B. Gruber, Heiner Boeing, Demetrius Albanes, Wen Yi Huang, Sergi Castellví-Bel, Jane C. Figueiredo, Catherine M. Tangen, Andrew T. Chan, Annika Lindblom, Deborah A. Nickerson, Richard B. Hayes, Lori C. Sakoda, Flavio Lejbkowicz, Salvatore Panico, Alicja Wolk, Kenneth Offit, John D. Potter, Leon Raskin, Bette J. Caan, Clemens Schafmayer, Mingyang Song, Lihong Qi, Elio Riboli, Hyun Min Kang, Sophia Harlid, Pavel Vodicka, Ludmila Vodickova, Cornelia M. Ulrich, Stephanie L. Schmit, Victor Moreno, Anna H. Wu, Brenda Diergaarde, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Mazda Jenab, Amit Joshi, Stefanie Brezina, Stephanie A. Bien, Charles Kooperberg, Shuji Ogino, Daniela Seminara, Graham Casey, Andrea N. Burnett-Hartman, Robert W. Haile, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Ross L. Prentice, Yi Lin, Antonio Agudo, Gonçalo R. Abecasis, Sonja I. Berndt, Stephen J. Chanock, Stéphane Bézieau, Patrick S. Parfrey, Richard Barfield, Marie-Christine Boutron-Ruault, Huyghe, Jeroen R [0000-0001-6027-9806], Brenner, Hermann [0000-0002-6129-1572], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hoffmeister, Michael [0000-0002-8307-3197], Huang, Wen-Yi [0000-0002-4440-3368], Jenab, Mazda [0000-0002-0573-1852], Murphy, Neil [0000-0003-3347-8249], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, Oncology, Candidate gene, Nutrition and Disease, Colorectal cancer, Genome-wide association study, Bioinformatics, medicine.disease_cause, Germline, colon carcinogenesis, Transcriptome, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, Age of Onset, Cecum, Aged, 80 and over, Gastroenterology, Middle Aged, cancer susceptibility, Primary tumor, Colon, Descending, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Medical Genetics, Colon, Transverse, Adult, medicine.medical_specialty, Colon, cancer genetics, colorectal cancer, Biology, Polymorphism, Single Nucleotide, White People, Colon, Ascending, Genetic Heterogeneity, Young Adult, 03 medical and health sciences, Age Distribution, Medicina preventiva, genetic polymorphisms, Colon, Sigmoid, Càncer colorectal, Internal medicine, medicine, Genetics, Humans, Alleles, VLAG, Genetic association, Medicinsk genetik, Aged, Global Nutrition, Preventive medicine, Wereldvoeding, Cancer och onkologi, Gastroenterology & Hepatology, Rectal Neoplasms, Cancer, 1103 Clinical Sciences, medicine.disease, digestive system diseases, 030104 developmental biology, Cancer and Oncology, Case-Control Studies, 1114 Paediatrics and Reproductive Medicine, Human genome, Carcinogenesis, Genètica, Genome-Wide Association Study
Abstract

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for sporadic CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48,214 CRC cases and 64,159 controls of European ancestry. We characterized effect heterogeneity at CRC risk loci using multinomial modeling.ResultsWe identified 13 loci that reached genome-wide significance (P−8) and that were not reported by previous GWAS for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumor.Significance of this studyWhat is already known about this subject?Heterogeneity among colorectal cancer (CRC) tumors originating at different locations of the colorectum has been revealed in somatic genomes, epigenomes, and transcriptomes, and in some established environmental risk factors for CRC.Genome-wide association studies (GWAS) have identified over 100 genetic variants for overall CRC risk; however, a comprehensive analysis of the extent to which genetic risk factors differ by the anatomical sublocation of the primary tumor is lacking.What are the new findings?In this large consortium-based study, we analyzed clinical and genome-wide genotype data of 112,373 CRC cases and controls of European ancestry to comprehensively examine whether CRC case subgroups defined by anatomical sublocation have distinct germline genetic etiologies.We discovered 13 new loci at genome-wide significance (P−8) that were specific to certain anatomical sublocations and that were not reported by previous GWAS for overall CRC risk; multiple lines of evidence support strong candidate target genes at several of these loci, including PTGER3, LCT, MLH1, CDX1, KLF14, PYGL, BCL11B, and BMP7.Systematic heterogeneity analysis of genetic risk variants for CRC identified thus far, revealed that the genetic architectures of proximal and distal CRC are partly distinct.Taken together, our results further support the idea that tumors arising in different anatomical sublocations of the colorectum may have distinct etiologies.How might it impact on clinical practice in the foreseeable future?Our results provide an informative resource for understanding the differential role that genes and pathways may play in the mechanisms of proximal and distal CRC carcinogenesis.The new insights into the etiologies of proximal and distal CRC may inform the development of new precision prevention strategies, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention.Our findings suggest that future studies of etiological risk factors for CRC and molecular mechanisms of carcinogenesis should take into consideration the anatomical sublocation of the colorectal tumor.

Published
2021

46. The Spanish revised interview for deteriorations in daily living activities in dementia 2: Everyday functioning needs in people with dementia in Colombia and Chile

Author

Ana Milena Gaviria, Tomas Leon, José Franco, Lorena Moreno Samaniego, Clarissa Giebel, and Mark Gabbay

Subjects
Gerontology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Activities of daily living, Developmental Neuroscience, Epidemiology, Health Policy, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, medicine.disease, Psychology
Published
2020

48. Performance Evaluation of Tight Ultrafiltration Membrane Systems at Pilot Scale for Agave Fructans Fractionation and Purification

Author

Enrique Arriola-Guevara, Rosa María Camacho-Ruiz, Rogelio Prado-Ramírez, Lorena Moreno-Vilet, and Noe Luiz-Santos

Subjects
Ultrafiltration, ceramic membrane, Filtration and Separation, 02 engineering and technology, Fractionation, 010501 environmental sciences, lcsh:Chemical technology, 01 natural sciences, rejection coefficient, Article, Fructan, polymeric membrane, Chemical Engineering (miscellaneous), lcsh:TP1-1185, lcsh:Chemical engineering, 0105 earth and related environmental sciences, Chromatography, Fouling, Chemistry, Process Chemistry and Technology, agave fructans, lcsh:TP155-156, Permeation, 021001 nanoscience & nanotechnology, Ceramic membrane, Membrane, Yield (chemistry), 0210 nano-technology, fine ultrafiltration
Abstract

Ceramic and polymeric membrane systems were compared at the pilot scale for separating agave fructans into different molecular weight fractions that help to diversify them into more specific industrial applications. The effect of the transmembrane pressure of ultrafiltration performance was evaluated through hydraulic permeability, permeate flux and rejection coefficients, using the same operating conditions such as temperature, feed concentration and the molecular weight cut-off (MWCO) of membranes. The fouling phenomenon and the global yield of the process were evaluated in concentration mode. A size distribution analysis of agave fructans is presented and grouped by molecular weight in different fractions. Great differences were found between both systems, since rejection coefficients of 68.6% and 100% for fructans with degrees of polymerization (DP) &gt, 10, 36.3% and 99.3% for fructooligosaccharides (FOS) and 21.4% and 34.2% for mono-disaccharides were obtained for ceramic and polymeric membrane systems, respectively. Thus, ceramic membranes are better for use in the fractionation process since they reached a purity of 42.2% of FOS with a yield of 40.1% in the permeate and 78.23% for fructans with DP &gt, 10 and a yield of 70% in the retentate. Polymeric membranes make for an efficient fructan purification process, eliminating only mono-disaccharides, and reaching a 97.7% purity (considering both fructan fractions) with a yield of 64.3% in the retentate.

Published
2020

49. Genetic Counseling for Hereditary Gastric and Pancreatic Cancer in High-Risk Gastrointestinal Cancer Clinics: An Effective Strategy

Author

Ariadna Sánchez, Cristina Herrera-Pariente, Gerhard Jung, Sabela Carballal, Lorena Moreno, Miriam Cuatrecasas, Antoni Castells, Rebeca Moreira, Mireia Díaz, Joan Llach, Maria Pellise, Liseth Rivero-Sánchez, Leticia Moreira, Francesc Balaguer, and Teresa Ocaña

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Genetic counseling, pancreatic cancer, lcsh:RC254-282, Genetic analysis, familial cancer, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Internal medicine, Pancreatic cancer, medicine, Gastrointestinal cancer, Family history, business.industry, gastric cancer, Cancer, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, hereditary cancer, 030220 oncology & carcinogenesis, Adenocarcinoma, 030211 gastroenterology & hepatology, business, genetic counselling
Abstract

The identification of high-risk groups of gastric (GC) and pancreatic adenocarcinoma (PC) due to a hereditary basis could imply a benefit in the affected families by establishing personalized preventive strategies. We aimed at assessing the diagnostic yield of GC/PC hereditary syndromes in individuals evaluated based on specific clinical criteria. In total, 77 unrelated individuals (45 from GC group/32 from PC group) were recruited: 51 (66.2%) cancer diagnosis &lt, 60 years, 3 (4%) with personal history of GC/PC and other cancer and 23 (29.8%) due to family history. Immunohistochemical analysis of DNA mismatch repair proteins was performed in 38 (49.3%) available tumors, being pathological in one (2%) GC. A genetic analysis was performed if clinical criteria of hereditary syndrome were fulfilled, identifying a mutation in 10/22 (45.5%) families [7/16 (43.7%) with GC and 3/6 (50%) with PC] and 19 (24.7%) fulfilled criteria of familial cancer. Diagnosis of cancer &lt, 40 years and personal history of other cancers were independent risk factors of a hereditary syndrome [OR:11.3 (95%IC 1.9&ndash, 67), p = 0.007 and OR:17.4 (95% IC 2.5&ndash, 119.9), p = 0.004, respectively]. The selection of patients based on clinical criteria leads to high diagnostic yield, detecting a causative germline mutation in almost half of the cases, therefore, both meticulous genetic counseling and use of multi-gen panels is crucial.

Published
2020

50. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author

Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]

Subjects
Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)

Published
2020

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