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1. Consensus statement on the use of alemtuzumab in daily clinical practice in Spain

Author

J E, Meca-Lallana, M, Fernández-Prada, E, García Vázquez, S, Moreno Guillén, S, Otero Romero, M, Rus Hidalgo, L M, Villar Guimerans, S, Eichau Madueño, Ó, Fernández Fernández, G, Izquierdo Ayuso, J C, Álvarez Cermeño, C, Arnal García, R, Arroyo González, L, Brieva Ruiz, C, Calles Hernández, A, García Merino, M, González Plata, M Á, Hernández Pérez, E, Moral Torres, J, Olascoaga Urtaza, P, Oliva-Nacarino, C, Oreja-Guevara, R, Ortiz Castillo, A, Oterino, J M, Prieto González, L, Ramió-Torrentá, A, Rodríguez-Antigüedad, A, Saiz, M, Tintoré, X, Montalbán Gairin, Institut Català de la Salut, [Meca-Lallana JE] CSUR Esclerosis Múltiple, Servicio de Neurología, Hospital Clínico Universitario Virgen de la Arrixaca (IMIB-ARRIXACA), Cátedra de Neuroinmunología Clínica y Esclerosis Múltiple, UCAM, Universidad Católica San Antonio, Murcia, Spain. [Fernández-Prada M] Servicio de Medicina Preventiva y Salud Pública, Hospital Vital Álvarez-Buylla, Mieres, Spain. [García Vázquez E] Servicio de MI-Infecciosas, Hospital Clínico Universitario Virgen de la Arrixaca, Departamento de Medicina, Facultad de Medicina, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain. [Moreno Guillén S] Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain. [Otero Romero S, Montalbán Gairin X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rus Hidalgo M] Servicio de Neurología, Hospital Virgen Macarena, Sevilla, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Multiple Sclerosis, Práctica clínica habitual, España, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Effectiveness, Antibodies, Monoclonal, Humanized, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized [CHEMICALS AND DRUGS], Multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Materials Chemistry, Humans, aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados [COMPUESTOS QUÍMICOS Y DROGAS], Alemtuzumab, Seguridad, Anticossos monoclonals - Ús terapèutic, Presa de decisions, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Psychological Phenomena::Mental Processes::Thinking::Decision Making::Consensus [PSYCHIATRY AND PSYCHOLOGY], Spain, Eficacia, Esclerosis múltiple, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Safety, fenómenos psicológicos::procesos mentales::pensamiento::toma de decisión::consenso [PSIQUIATRÍA Y PSICOLOGÍA], Esclerosi múltiple - Tractament, Daily clinical practice
Abstract

Alemtuzumab; Eficacia; Práctica clínica habitual Alemtuzumab; Effectiveness; Daily clinical practice Alemtuzumab; Eficàcia; Pràctica clínica habitual Introduction Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. Objective A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. Development A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. Conclusion The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice. Introducción Alemtuzumab es un fármaco de alta eficacia aprobado por la Agencia Europea de Medicamentos como tratamiento modificador de la enfermedad en pacientes con esclerosis múltiple remitente recurrente. Objetivo Elaborar un documento de consenso sobre el manejo de alemtuzumab en la práctica clínica habitual, que sea de aplicación en el ámbito español. Desarrollo Un grupo de expertos en esclerosis múltiple revisó las publicaciones disponibles hasta diciembre de 2017, de tratamiento con alemtuzumab y esclerosis múltiple. Se incluyeron trabajos sobre eficacia, efectividad y seguridad, despistaje de infecciones y vacunación, administración y monitorización. La propuesta inicial de recomendaciones fue desarrollada por un grupo coordinador con base en la evidencia disponible y en su experiencia clínica. El proceso de consenso se llevó a cabo en 2 etapas; se estableció como porcentaje inicial de acuerdo grupal el 80%. El documento final con todas las recomendaciones acordadas por el grupo de trabajo se sometió a revisión externa y los comentarios recibidos fueron considerados por el grupo coordinador. Conclusiones El documento aportado pretende ser una herramienta útil para facilitar el manejo del fármaco en condiciones de práctica clínica habitual. Sanofi-Genzyme provided financial support to this project.

Published
2022

2. KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Author

Jerónimo Martínez-García, Emilio M. Serrano-López, Jorge A. Martínez-Escribano, María D. Martínez-Hernández, María V. Martínez-Sánchez, Alfredo Minguela, Senena Corbalán-García, Francisco García-Cózar, Lourdes Gimeno, María A. Cánovas-Zapata, María F Soto-Ramírez, María R. Álvarez-López, O. S. Acuña, Pedro López-Cubillana, José A. Campillo, Biomedicina, Biotecnología y Salud Pública, [Gimeno,L, Campillo,JA, Cánovas-Zapata,MA, Martínez-Sánchez,MV, Martínez-Hernández,MD, Soto-Ramírez,MF, Álvarez-López,MR, Minguela,A] Immunology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Gimeno,L] Human Anatomy Department, University of Murcia (UM), Murcia, Spain. [Serrano-López,EM, Corbalan-García,S] Department of Biochemistry and Molecular Biology, Veterinary School, International Excellence Campus 'Campus Mare Nostrum', Universidad Murcia, Murcia, Spain. [Serrano-López,EM, Corbalan-García,S] Biomembranes and Cell Signaling, Instituto Murciano de Investigación Biomédica, Murcia, Spain. [Acuña,OS] Faculty of Veterinary and Zootechnics, Autonomous University of Sinaloa (UAS), Culiacan, Mexico. [Acuña,OS] Department of Research, Animal Reproduction Biotechnology (ARBiotech), Culiacan, Mexico. [García-Cózar,F] Department of Biomedicine, Biotechnology and Public Health (Immunology), University of Cadiz and Institute of Biomedical Research Cádiz (INIBICA), Cadiz, Spain. [López-Cubillana,P] Urology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Martínez-Escribano,J] Dermatology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Martínez-García,J] Oncology Service, Hospital Clínico Universitario Virgen de la Arrixaca and Instituto Murciano de Investigación Biomédica (IMIB-Arrixaca), Murcia, Spain. [Álvarez-López,MR] Faculty of Health Sciences, Universidad Católica San Antonio de Murcia, UCAM, Murcia, Spain., and This research was funded by the Spanish Ministry of Economy—Institute of Health Carlos III (PI1302297), Fundación Mutua Madrileña (AP74392010), and Fundación Séneca de la Agencia de Ciencia y Tecnología, Región de Murcia, (20812-PI-18). M.V. Martínez-Sánchez was funded by the Asociación Pablo Ugarte (APU).

Subjects
0301 basic medicine, Cancer Research, immunosurveillance, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Monitoring, Physiologic::Monitoring, Immunologic [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Cytotoxic T cell, Vigilancia inmunológica, Linfocitos T, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasias, CD8+T cells, KIR, Immunosurveillance, medicine.anatomical_structure, Oncology, Tumor microenvironment, 030220 oncology & carcinogenesis, Análisis de secuencia por matrices de oligonucleótidos, microarray, T cell, Cells, chemical and pharmacologic phenomena, Biology, CD8+ T cells, lcsh:RC254-282, Article, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription, Genetic::Transcriptome [Medical Subject Headings], 03 medical and health sciences, T Lymphocytes, Immune system, KIR2DL1, Células, Microambiente tumoral, medicine, cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Histologic Type::Nevi and Melanomas::Melanoma [Medical Subject Headings], Receptores KIR, Cancer, Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [Medical Subject Headings], CD8+T, medicine.disease, Gene expression profiling, 030104 developmental biology, Cancer research, gene expression, CD8, Expresión génica, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD8-Positive T-Lymphocytes [Medical Subject Headings]
Abstract

Simple Summary Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. Abstract Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

Published
2020

3. Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study

Author

Anja M. Sedlmeier, Vivian Viallon, Pietro Ferrari, Laia Peruchet-Noray, Emma Fontvieille, Amina Amadou, Nazlisadat Seyed Khoei, Andrea Weber, Hansjörg Baurecht, Alicia K. Heath, Kostas Tsilidis, Rudolf Kaaks, Verena Katzke, Elif Inan-Eroglu, Matthias B. Schulze, Kim Overvad, Catalina Bonet, Esther Ubago-Guisado, María-Dolores Chirlaque, Eva Ardanaz, Aurora Perez-Cornago, Valeria Pala, Rosario Tumino, Carlotta Sacerdote, Fabrizio Pasanisi, Kristin B. Borch, Charlotta Rylander, Elisabete Weiderpass, Marc J. Gunter, Béatrice Fervers, Michael F. Leitzmann, Heinz Freisling, [Sedlmeier, Anja M. M.] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Weber, Andrea] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Baurecht, Hansjoerg] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Leitzmann, Michael F. F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany, [Viallon, Vivian] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Ferrari, Pietro] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Peruchet-Noray, Laia] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Fontvieille, Emma] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Weiderpass, Elisabete] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Gunter, Marc J. J.] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Freisling, Heinz] Int Agcy Res Canc IARC, Nutr & Metab Branch, Lyon, France, [Peruchet-Noray, Laia] Univ Barcelona, Fac Med, Dept Clin Sci, Barcelona, Spain, [Amadou, Amina] Ctr Leon Berard, Dept Prevent Canc Environm, Lyon, France, [Fervers, Beatrice] Ctr Leon Berard, Dept Prevent Canc Environm, Lyon, France, [Amadou, Amina] INSERM, UMR1296 Radiat Def, Hlth, Environm, Lyon, France, [Fervers, Beatrice] INSERM, UMR1296 Radiat Def, Hlth, Environm, Lyon, France, [Seyed Khoei, Nazlisadat] Univ Vienna, Fac Life Sci, Dept Nutr Sci, Vienna, Austria, [Heath, Alicia K. K.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Tsilidis, Kostas] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Tsilidis, Kostas] Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece, [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Katzke, Verena] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Inan-Eroglu, Elif] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany, [Schulze, Matthias B. B.] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany, [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark, [Bonet, Catalina] Catalan Inst Oncol ICO, Unit Nutr & Canc, Barcelona, Spain, [Bonet, Catalina] Bellvitge Biomed Res Inst IDIBELL, Canc Prevent & Palliat Care Program, Nutr & Canc Grp, Epidemiol,Publ Hlth, Barcelona, Spain, [Ubago-Guisado, Esther] Escuela Andaluza Salud Publ EASP, Granada, Spain, [Ubago-Guisado, Esther] Inst Invest Biosanitaria Ibs GRANADA, Granada, Spain, [Ubago-Guisado, Esther] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, Maria-Dolores] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Ardanaz, Eva] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, Maria-Dolores] Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Chirlaque, Maria-Dolores] Murcia Univ, IMIB Arrixaca, Murcia, Spain, [Ardanaz, Eva] IdiSNA, Navarra Publ Hlth Inst, Pamplona, Spain, [Perez-Cornago, Aurora] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England, [Pala, Valeria] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy, [Tumino, Rosario] AIRE ONLUS, Hyblean Assoc Epidemiol Res, Ragusa, Italy, [Sacerdote, Carlotta] Citta Salute & Sci Univ Hosp, Unit Canc Epidemiol, Turin, Italy, [Pasanisi, Fabrizio] Feder II Univ Hosp, Dept Clin Med & Surg, Clin Nutr Unit, Naples, Italy, [Borch, Kristin B. B.] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Commun Med, Tromso, Norway, [Rylander, Charlotta] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Commun Med, Tromso, Norway, French National Cancer Institute (l'Institut National du Cancer), International Agency for Research on Cancer (IARC), Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society (Denmark), Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (INSERM) (France), German Cancer Aid (Germany), German Cancer Research Center (DKFZ) (Germany), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy (Italy), Compagnia di San Paolo (Italy), National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands), Netherlands Cancer Registry (NKR) (The Netherlands), LK Research Funds (The Netherlands), Dutch Prevention Funds (The Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands), World Cancer Research Fund (WCRF) (The Netherlands), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain), Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society (Sweden), Swedish Research Council (Sweden), County Council of Skane (Sweden), County Council of Vaesterbotten (Sweden), Cancer Research UK (United Kingdom), and Medical Research Council (United Kingdom)

Subjects
Cancer Research, Oncology, Height, Fat, Physical-activity, Obesity, Esophageal, Adenocarcinoma, Metaanalysis, Weight, Nutrition, Validity
Abstract

Background Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. Methods We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35–65 years at recruitment (1990–2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30–1.42) for endometrial cancer to 1.08 (1.03–1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02–1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03–1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99–1.01). Conclusions In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

Published
2022

4. Alcoholic Beverage Preference and Dietary Habits in Elderly across Europe: Analyses within the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) Project

Author

Olov Rolandsson, Christina Bamia, José María Huerta, Oscar H. Franco, Mark G. O'Doherty, Lisette C. P. G. M. de Groot, Antonia Trichopoulou, Nicole Jankovic, Daan Kromhout, Jolanda M. A. Boer, Heidi P. Fransen, Begona Martinez, Jessica C. Kiefte-de Jong, Diewertje Sluik, Paolo Boffetta, Jean Ferrières, Ben Schöttker, Anouk Geelen, Sture Eriksson, Edith J. M. Feskens, Frank Kee, Sluik, D., Jankovic, N., O'Doherty, M.G., Geelen, A., Schöttker, B., Rolandsson, O., Kiefte-De Jong, J.C., Ferrieres, J., Bamia, C., Fransen, H.P., Boer, J.M.A., Eriksson, S., Martínez, B., Huerta, J.M., Kromhout, D., De Groot, L.C.P.G.M., Franco, O.H., Trichopoulou, A., Boffetta, P., Kee, F., Feskens, E.J.M., [Sluik, Diewertje] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [Jankovic, Nicole] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [Geelen, Anouk] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [Kromhout, Daan] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [de Groot, Lisette C. P. G. M.] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [Feskens, Edith J. M.] Wageningen Univ, Div Human Nutr, Wageningen, Netherlands, [Jankovic, Nicole] Univ Duisburg Essen, Fac Med, Ctr Clin Epidemiol, Inst Med Informat Biometry & Epidemiol, Essen, Germany, [O'Doherty, Mark G.] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland, [Kee, Frank] Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland, [Schoettker, Ben] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany, [Schoettker, Ben] FOM Univ, Inst Hlth Care & Social Sci, Essen, Germany, [Rolandsson, Olov] Umea Univ, Dept Publ Hlth & Clin Med, Family Med, Umea, Sweden, [Eriksson, Sture] Umea Univ, Dept Publ Hlth & Clin Med, Family Med, Umea, Sweden, [Kiefte-de Jong, Jessica C.] Leiden Univ Coll, Global Publ Hlth, The Hague, Netherlands, [Kiefte-de Jong, Jessica C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands, [Franco, Oscar H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands, [Ferrieres, Jean] Toulouse Univ, Sch Med, Dept Cardiol, Toulouse, France, [Bamia, Christina] Hellen Hlth Fdn, Athens, Greece, [Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece, [Boffetta, Paolo] Hellen Hlth Fdn, Athens, Greece, [Bamia, Christina] Univ Athens, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Nutr & Hlth,Sch Med, Athens, Greece, [Trichopoulou, Antonia] Univ Athens, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Nutr & Hlth,Sch Med, Athens, Greece, [Fransen, Heidi P.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands, [Boer, Jolanda M. A.] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands, [Martinez, Begona] Univ Granada, Hosp Univ Granada, Escuela Andaluza Salud Publ, Inst Invest Biosanitaria Ibs Granada, Granada, Spain, [Martinez, Begona] CIBER Epidemiol Salud Publ CIBERESP, Madrid, Spain, [Maria Huerta, Jose] CIBER Epidemiol Salud Publ CIBERESP, Madrid, Spain, [Maria Huerta, Jose] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Boffetta, Paolo] Mt Sinai Sch Med, Icahn Sch Med, New York, NY USA, European Foundation for Alcohol Research (ERAB), Dutch Beer Institute, FP7 framework programme of the Directorate General for Research & Innovation in the European Commission, Health Research Fund (FIS) of the Spanish Ministry of Health (Spain), CIBER de Epidemiologia y Salud Publica (CIBERESP), Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, Navarra (Spain), Medical Research Council, [Sluik,D, Jankovic,N, Geelen,A, Kromhout,D, Groo,LPCGM, Feskens,EJM] Division of Human Nutrition, Wageningen University, Wageningen, the Netherland. [Jankovic,N] Centre of Clinical Epidemiology, Institute for Medical Informatics, Biometry and Epidemiology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany. [O’Doherty,MG, Kee,F] UKCRC Centre of Excellence for Public Health, Queens University Belfast, Belfast, Northern Ireland. [Schöttker,B] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Institute of Health Care and Social Sciences, FOM University, Essen, Germany. [Rolandsson,O, Eriksson,S] Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden. [Kiefte-de Jong,JC] Global Public Health, Leiden University College, the Hague, the Netherlands. [Kiefte-de Jong,JC, Franco,OH] Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. [Ferrieres,J] Department of Cardiology, Toulouse University School of Medicine, Toulouse, France. [Bamia,C, Trichopoulou,A, Boffetta,P] Hellenic Health Foundation, Athens, Greece. [Bamia,C, Trichopoulou,A] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Fransen,HP] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. [Boer,JMA] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [Martínez,B] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada, Hospitales Universitaios de Granada/Universidad de Granada, Granada, Spain. [Martínez,B, Huerta,JM] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Boffetta,P] Icahn School of Medicine, Mount Sinai School of Medicine, New York, United States of America., The work of DS was supported by the European Foundation for Alcohol Research (ERAB) and the Dutch Beer Institute. The sponsor did not have any role in the design and conduct of the study, collection, management, analysis and interpretation of the data, and preparation, review or approval of the manuscript. This analysis was part of the Consortium on Health and Ageing (CHANCES) project funded in the FP7 framework programme of the DirectorateGeneral for Research & Innovation in the European Commission (grant 242244). The CHANCES project is coordinated by the Hellenic Health Foundation, Greece. The EPIC-Elderly Study was partially supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Spain), the CIBER de Epidemiología y Salud Pública (CIBERESP), and the Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra (Spain), and Epidemiology

Subjects
Male, Aging, General Practice, Wine, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Beer [Medical Subject Headings], 0302 clinical medicine, Elderly, Surveys and Questionnaires, lcsh:Science, Determinants, Human Nutrition & Health, Geriatrics, Aged, 80 and over, Drinking patterns, Humane Voeding & Gezondheid, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Beer, food and beverages, Lipids, Humanos, 3. Good health, Näringslära, Life-style, Cerveza, Dieta, Estados unidos, Enfermedades cardiovasculares, Geographicals::Geographic Locations::Americas::North America::United States [Medical Subject Headings], Factores de riesgo, Cohort study, medicine.medical_specialty, Alcohol Drinking, Anciano, Consumption patterns, Guidelines, Social class, 03 medical and health sciences, Humans, Diseases::Cardiovascular Diseases [Medical Subject Headings], Life Style, Aged, VLAG, Global Nutrition, Wereldvoeding, Ethanol, lcsh:R, Biology and Life Sciences, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Wine [Medical Subject Headings], Allmänmedicin, 030104 developmental biology, Social Class, lcsh:Q, Observational study, Population Groupings, 0301 basic medicine, Gerontology, Multivariate statistics, Nutrition and Disease, Medizin, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Fats, Rotterdam Study, Voeding en Ziekte, Medicine and Health Sciences, 030212 general & internal medicine, Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages [Medical Subject Headings], 2. Zero hunger, Multidisciplinary, Alcohol Consumption, Nutrition and Dietetics, Alcoholic Beverages, Vino, Middle Aged, Bebidas alcohólicas, Preference, Europe, Hábitos alimenticios, Female, Research Article, Alcoholic beverage - cardiovascular risk, Population, Spirits, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Beverages, Food Preferences, Environmental health, medicine, Life Science, Europa (Continente), Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Mortality, Nutrition, business.industry, Feeding Behavior, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior::Food Habits [Medical Subject Headings], Diet, Age Groups, People and Places, business
Abstract

Introduction: The differential associations of beer, wine, and spirit consumption on cardiovascular risk. Alcoholic beverage preference and dietary habits in elderly across Europe: Analyses within the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) project found in observational studies may be confounded by diet. We described and compared dietary intake and diet quality according to alcoholic beverage preference in European elderly. Methods: From the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES), seven European cohorts were included, i.e. four sub-cohorts from EPIC-Elderly, the SENECA Study, the Zutphen Elderly Study, and the Rotterdam Study. Harmonized data of 29,423 elderly participants from 14 European countries were analyzed. Baseline data on consumption of beer, wine, and spirits, and dietary intake were collected with questionnaires. Diet quality was assessed using the Healthy Diet Indicator (HDI). Intakes and scores across categories of alcoholic beverage preference (beer, wine, spirit, no preference, non-consumers) were adjusted for age, sex, socio-economic status, self-reported prevalent diseases, and lifestyle factors. Cohort-specific mean intakes and scores were calculated as well as weighted means combining all cohorts. Results: In 5 of 7 cohorts, persons with a wine preference formed the largest group. After multivariate adjustment, persons with a wine preference tended to have a higher HDI score and intake of healthy foods in most cohorts, but differences were small. The weighted estimates of all cohorts combined revealed that non-consumers had the highest fruit and vegetable intake, followed by wine consumers. Non-consumers and persons with no specific preference had a higher HDI score, spirit consumers the lowest. However, overall diet quality as measured by HDI did not differ greatly across alcoholic beverage preference categories. Discussion: This study using harmonized data from ~30,000 elderly from 14 European countries showed that, after multivariate adjustment, dietary habits and diet quality did not differ greatly according to alcoholic beverage preference. © 2016 Sluik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Published
2016

5. Regulation of TFPIα expression by miR-27a/b-3p in human endothelial cells under normal conditions and in response to androgens

Author

Chary López-Pedrera, Nuria García-Barberá, Ginés Luengo-Gil, Rocío González-Conejero, Carlos Perez-Sanchez, Salam Salloum-Asfar, John-Bjarne Hansen, Vicente Vicente, Constantino Martínez, Ana B. Arroyo, Raúl Teruel-Montoya, Silvia Navarro, Vanessa Roldán, [Arroyo, Ana B.] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Salloum-Asfar, Salam] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Teruel-Montoya, Raul] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Garcia-Barbera, Nuria] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Luengo-Gil, Gines] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Roldan, Vanessa] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Vicente, Vicente] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Gonzalez-Conejero, Rocio] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Martinez, Constantino] Univ Murcia, Ctr Reg Hemodonac, IMIB Arrixaca, Murcia, Spain, [Perez-Sanchez, Carlos] Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Inst Res Biomed Cordoba IMIBIC, Cordoba, Spain, [Lopez-Pedrera, Chary] Univ Cordoba, Reina Sofia Univ Hosp, Maimonides Inst Res Biomed Cordoba IMIBIC, Cordoba, Spain, [Navarro, Silvia] Hosp Univ & Politecn La Fe, Med Res Inst, Valencia, Spain, [Hansen, John-Bjarne] UiT Arctic Univ Norway, Dept Clin Med, KG Jebsen Thrombosis Res & Expertise Ctr TREC, Tromso, Norway, [Hansen, John-Bjarne] Univ Hosp North Norway, Div Internal Med, Tromso, Norway, Fondo Europeo de Desarrollo Regional (FEDER), University of Murcia, and Instituto de Salud Carlos III

Subjects
0301 basic medicine, Risk, medicine.medical_specialty, Inhibitor, Lipoproteins, Mirnas, 030204 cardiovascular system & hematology, Biology, Models, Biological, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Cardiovascular-disease, Genes, Reporter, Internal medicine, microRNA, medicine, Humans, Testosterone, RNA, Messenger, Mortality, 3' Untranslated Regions, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Cardiology: 771, Regulation of gene expression, Multidisciplinary, Binding Sites, Tissue factor pathway, Molecular medicine, Endothelial Cells, Men, Thrombosis, Endothelial stem cell, MicroRNAs, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Dihydrotestosterone, Androgens, RNA Interference, Ex vivo, Hormone, medicine.drug
Abstract

The increased risk of cardiovascular events in older men is multifactorial, but the significant reduction of testosterone levels has been involved. As this hormone regulates the expression of TFPI by unknown mechanisms, we aimed to evaluate the role of miRNAs in the regulation of TFPIα expression under normal conditions and in response to androgens. In silico studies allowed the selection of 4 miRNAs as potential TFPIα regulators. Only miR-27a/b-3p significantly reduced TFPIα expression in two endothelial cell lines. Luciferase assays demonstrated a direct interaction between miR-27a/b-3p and TFPI 3′UTR. Ex vivo analysis of TFPI and miRNA levels in 74 HUVEC samples from healthy subjects, showed a significant and inverse correlation between TFPI and miR-27a-3p. Moreover, anticoagulant activity of TFPIα from cells supernatants decreased ~30% with miR-27a/b-3p and increased ~50% with anti-miR-27a/b-3p. Interestingly, treatment of EA.hy926 with a physiological dose of dihydrotestosterone (30 nM) significantly increased (~40%) TFPIα expression with a parallel decreased (~50%) of miR-27a/b-3p expression. In concordance, increased levels of miR-27a/b-3p normalized the up-regulation induced by testosterone. Our results suggest that testosterone is a hinge in miR-27/TFPIα regulation axis. Future studies are needed to investigate whether testosterone variations are involved in a miR-27/TFPIα dysregulation that could increase the cardiovascular risk.

Published
2015

6. Determination of oleanolic acid in human plasma and its association with olive oil intake in healthy Spanish adults within the EPIC Spain cohort study

Author

Miguel Rodríguez-Barranco, Noémie Travier, Eva Ardanaz, Genevieve Buckland, José Ramón Quirós, Carlos A. González, Aurelio Barricarte, Miren Dorronsoro, Rafael de la Torre, Carmen Navarro, Antoni Pastor, María José Sánchez, Maria Dolores Chirlaque, Pilar Amiano, Amaia Molinuevo, Antonio Agudo, José María Huerta, Leila Lujan-Barroso, [Buckland, Genevieve] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr & Canc, Barcelona, Spain, [Lujan-Barroso, Leila] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr & Canc, Barcelona, Spain, [Alberto Gonzalez, Carlos] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr & Canc, Barcelona, Spain, [Travier, Noemie] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr & Canc, Barcelona, Spain, [Agudo, Antonio] Catalan Inst Oncol ICO IDIBELL, Canc Epidemiol Res Programme, Unit Nutr & Canc, Barcelona, Spain, [Pastor, Antoni] Hosp del Mar, IMIM, Neurosci Res Program, Integrat Pharmacol & Syst Neurosci Res Grp,Med Re, Barcelona, Spain, [de la Torre, Rafael] Hosp del Mar, IMIM, Neurosci Res Program, Integrat Pharmacol & Syst Neurosci Res Grp,Med Re, Barcelona, Spain, [Pastor, Antoni] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela, Spain, [de la Torre, Rafael] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela, Spain, [Lujan-Barroso, Leila] Univ Barcelona, Sch Nursing, Dept Nursing Publ Hlth Mental Hlth & Matern & Chi, Barcelona, Spain, [Amiano, Pilar] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Maria Huerta, Jose] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Navarro, Carmen] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Dolores Chirlaque, Maria] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Sanchez, Maria-Jose] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Barricarte, Aurelio] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Ardanaz, Eva] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Dorronsoro, Miren] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Molinuevo, Amaia] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Amiano, Pilar] BioDonostia Res Inst, Publ Hlth Div Gipuzkoa, Donostia San Sebastian, Spain, [Dorronsoro, Miren] BioDonostia Res Inst, Publ Hlth Div Gipuzkoa, Donostia San Sebastian, Spain, [Maria Huerta, Jose] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Navarro, Carmen] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Dolores Chirlaque, Maria] IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Navarro, Carmen] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain, [Dolores Chirlaque, Maria] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain, [Sanchez, Maria-Jose] Inst Invest Biosanitaria Ibs, Andaluzian Sch Publ Hlth, Granada, Spain, [Rodriguez-Barranco, Miguel] Inst Invest Biosanitaria Ibs, Andaluzian Sch Publ Hlth, Granada, Spain, [Barricarte, Aurelio] Navarra Publ Hlth Inst, Dept Epidemiol, Pamplona, Spain, [Ardanaz, Eva] Navarra Publ Hlth Inst, Dept Epidemiol, Pamplona, Spain, [Barricarte, Aurelio] Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain, [Ardanaz, Eva] Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain, [Ramon Quiros, Jose] Publ Hlth & Hlth Planning Directorate, Asturias, Spain, [de la Torre, Rafael] Pompeu Fabra Univ UPF, Dept Expt & Hlth Sci DCEXS, Barcelona, Spain, AGAUR, Generalitat de Catalunya, Health Research Funds, FEDER funds /European Regional Development Fund (ERDF) 'A way to buid Europe', Spanish Regional Government of Andalusia, Spanish Regional Government of Asturias, Spanish Regional Government of Basque Country, Spanish Regional Government of Murcia, Spanish Regional Government of Navarra, Catalan Institute of Oncology (ICO-IDIBELL), and CIBER Epidemiologia y Salud Publica (CIBERESP)

Subjects
Adult, Male, Risk, 0301 basic medicine, Population, Apoptosis, Oli d'oliva -- Aspectes nutricionals, Project, Disposition, EPIC, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Animal science, Humans, EPIC cohort study, Medicine, Hydroxytyrosol, 030212 general & internal medicine, education, Oleanolic acid, Aged, Cancer, education.field_of_study, 030109 nutrition & dietetics, business.industry, Biomarker, Middle Aged, Nutrition Surveys, Triterpenes, European Prospective Investigation into Cancer and Nutrition, Biotechnology, chemistry, Spain, Human plasma, Cohort, Female, business, Olive oil, Food Science, Cohort study
Abstract

cope Oleanolic acid (OA) is an important triterpenic compound found in olive oil, however little is known about its concentrations in human plasma. We aimed to determine plasma OA levels in a healthy Spanish population and compare them with estimates of dietary olive oil intake. Methods and results The final study sample included 141 individuals randomly selected from the European Prospective Investigation into Cancer and Nutrition Spanish cohort. Dietary olive oil intake was estimated using validated dietary history questionnaires. OA concentrations were determined in plasma (from the participants’ stored blood samples) using a HPLC-MS method. Correlation coefficients between OA and olive oil intake were calculated, adjusting for center; sex; age; consumption of olives, apples, grapes, and red wine; and fasting state. The mean OA concentration in olive oil nonconsumers was 0.72 ng/mL (SD 0.82), while in the high olive oil intake group it was 1.32 ng/mL (SD 1.14). The fully adjusted partial Spearman correlations coefficients reached 0.36 (p-value < 0.001) overall, varying minimally by sex and fasting state. Conclusion This is the first study providing steady-state concentrations of triterpenes in humans. The results show that there was low-to-moderate correlation between OA concentrations and olive oil intake in this population.

Published
2017

7. Consensus on early detection of disease progression in patients with multiple sclerosis

Author

Meca-Lallana, José E, Casanova, Bonaventura, Rodríguez-Antigüedad, Alfredo, Eichau, Sara, Izquierdo, Guillermo, Durán, Carmen, Río, Jordi, Hernández, Miguel Ángel, Calles, Carmen, Prieto-González, José M, Ara, José Ramón, Uría, Dionisio F, Costa-Frossard, Lucienne, García-Merino, Antonio, Oreja-Guevara, Celia, Institut Català de la Salut, [Meca-Lallana JE] CSUR Multiple Sclerosis and Clinical Neuroimmunology Unit, Neurology Department, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain. [Casanova B] Department of Neurology, Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Rodríguez-Antigüedad A] Department of Neurology, Hospital Universitario Cruces, Barakaldo, Spain. [Eichau S] Department of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Izquierdo G] Fundación DINAC, Sevilla, Spain. [Durán C] Department of Neurology, Hospital Universitario de Badajoz, Badajoz, Spain. [Río J] Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
secondary progressive multiple sclerosis, Otros calificadores::/diagnóstico [Otros calificadores], Presa de decisions, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], multiple sclerosis, Esclerosi múltiple - Prognosi, Psychological Phenomena::Mental Processes::Thinking::Decision Making::Consensus [PSYCHIATRY AND PSYCHOLOGY], afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad [ENFERMEDADES], disease progression, Neurology, consensus, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Esclerosi múltiple - Diagnòstic, Other subheadings::/diagnosis [Other subheadings], Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [DISEASES], Neurology (clinical), fenómenos psicológicos::procesos mentales::pensamiento::toma de decisión::consenso [PSIQUIATRÍA Y PSICOLOGÍA], early detection
Abstract

Consensus; Early detection; Secondary progressive multiple sclerosis Consenso; Detección precoz; Esclerosis múltiple progresiva secundaria Consens; Detecció precoç; Esclerosi múltiple progressiva secundària Background: Early identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) can be challenging for clinicians, as diagnostic criteria for SPMS are primarily based on physical disability and a holistic interpretation. Objective: To establish a consensus on patient monitoring to identify promptly disease progression and the most useful clinical and paraclinical variables for early identification of disease progression in MS. Methods: A RAND/UCLA Appropriateness Method was used to establish the level of agreement among a panel of 15 medical experts in MS. Eighty-three items were circulated to the experts for confidential rating of the grade of agreement and recommendation. Consensus was defined when ≥66% agreement or disagreement was achieved. Results: Consensus was reached in 72 out of 83 items (86.7%). The items addressed frequency of follow-up visits, definition of progression, identification of clinical, cognitive, and radiological assessments as variables of suspected or confirmed SPMS diagnosis, the need for more accurate assessment tools, and the use of promising molecular and imaging biomarkers to predict disease progression and/or diagnose SPMS. Conclusion: Consensus achieved on these topics could guide neurologists to identify earlier disease progression and to plan targeted clinical and therapeutic interventions during the earliest stages of SPMS. This work was supported by Novartis. Meetings, data analysis, and medical writing assistance were funded by Novartis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2022
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8. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author

Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.

Subjects
Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL

Published
2021

9. A multicriteria decision analysis (MCDA) applied to three long-term prophylactic treatments for hereditary angioedema in Spain

Author

Néboa Zozaya, Teresa Caballero, Teresa González-Quevedo, Pedro Gamboa Setien, M. Ángeles González, Ramón Jódar, José Luis Poveda-Andrés, Encarna Guillén-Navarro, Agustín Rivero Cuadrado, Álvaro Hidalgo-Vega, [Zozaya, Neboa] Weber, Madrid, Spain, [Caballero, Teresa] Hosp Univ La Paz, Serv Alergol, Madrid, Spain, [Caballero, Teresa] Hosp La Paz, Inst Hlth Res IdiPaz, Madrid, Spain, [Caballero, Teresa] Ctr Biomed Res Network Rare Dis CIBERER U754, Madrid, Spain, [Gonzalez-Quevedo, Teresa] Hosp Univ Virgen del Rocio, Unidad Alergol, Unidad Referencia Angioedema Andalucia, Seville, Spain, [Gamboa Setien, Pedro] Hosp Univ Cruces, Unidad Alergol, Bizcaia, Spain, [Angeles Gonzalez, Ma] Hosp Univ La Paz, Serv Farm, Madrid, Spain, [Jodar, Ramon] Hosp Univ Bellvitge, Serv Farm, Barcelona, Spain, [Luis Poveda-Andres, Jose] Hosp Univ & Politecn La Fe, Serv Farm Hosp, Valencia, Spain, [Guillen-Navarro, Encarna] IMIB Arrixaca Univ Murcia, CIBERER ISCIII, Hosp Clin Univ Virgen de la Arrixaca, Secc Genet Med,Serv Pediadria, Murcia, Spain, [Cuadrado, Agustin Rivero] Hosp Univ La Paz, Madrid, Spain, [Hidalgo-Vega, Alvaro] Fdn Weber, Madrid, Spain, and [Hidalgo-Vega, Alvaro] Univ Castilla La Mancha, Toledo, Spain

Subjects
Hereditary angioedema, Methodological framework, Health Policy, Multicriteria decision analysis (MCDA), Hta, Drug testing, Lanadelumab, Technologies, Assaigs clínics de medicaments, Rare diseases, Medicines, Malalties hereditàries, Medical technology, Malalties rares, R855-855.5, Drugs evaluation, Rare disease, Genetic diseases
Abstract

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LIP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.240.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE.

Published
2022

10. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author

Ubago-Guisado, Esther, Rodríguez-Barranco, Miguel, Ching-López, Ana, Petrova, Dafina, Molina-Montes, Esther, Amiano, Pilar, Barricarte-Gurrea, Aurelio, Chirlaque, María-Dolores, Agudo, Antonio, Sánchez, María-José, [Ubago-Guisado,E, Rodríguez-Barranco,M, Ching-López,A, Petrova,D, Sánchez,MJ] Cancer Registry of Granada, Escuela Andaluza de Salud Pública, Granada, Spain. [Ubago-Guisado,E, Molina-Montes,E, Amiano,P, Barricarte-Gurrea,A, Chirlaque,MD, Sánchez,MJ] Epidemiology and Control of Chronic Diseases, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Ubago-Guisado,E, Sánchez,MJ] Cancer Epidemiology Group, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Petrova,D] Department of Experimental Psychology, Mind, Brain and Behavior Research Center (CIMCYC), University of Granada, Granada, Spain. [Molina-Montes,E] Department of Nutrition and Food Science, Campus of Cartuja, University of Granada, Granada, Spain. [Molina-Montes,E] Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Barricarte-Gurrea,A] Navarra Public Health Institute, Pamplona, Spain. [Barricarte-Gurrea,A] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain. [Agudo,A] Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L’Hospitalet de Llobregat, Spain. [Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain., and E.U.-G. is supported by the Programa Operativo Fondo Social Europeo (FSE) de Andalucía (2014–2020) and Junta de Andalucía (reference DOC_01618).

Subjects
Metaanalisis, Frutas, Meat, Neoplasias de la próstata, Neoplasias pulmonares, Etanol, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings], Carne, Fruits, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Ingestión de alimentos, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Breast cancer, Neoplasias colorrectales, Vegetables, Prospective Studies, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Prostate cancer, Revisión sistemática, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena [Medical Subject Headings], Colorectal cancer, Fish, Verduras, Neoplasias de la mama, Intake, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], Lung cancer, Alcohol
Abstract

The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies. Yes

Published
2021

11. Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance

Author

Bruno Ramos-Molina, Wilfredo Oliva-Olivera, María Isabel Queipo-Ortuño, Daniel Castellano-Castillo, Luis Ocaña-Wilhelmi, Fernando Cardona, [Castellano-Castillo,D, Oliva-Olivera,W] Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain. [Ramos-Molina,B] Grupo de Obesidad y Metabolismo, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain. [Ocaña-Wilhelmi,L] Unidad de Cirugía Metabólica, Hospital Clínico Virgen de la Victoria, Málaga, Spain. [Queipo-Ortuño,MI] Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, Málaga, Spain. [Cardona,F] UGC Pediatría, Instituto de Investigación Biomédica de Málaga, Hospital Regional de Málaga, Málaga, Spain. [Cardona,F] Department of Surgical Specialties, Biochemistry and Immunology School of Medicine, University of Malaga, Málaga, Spain., and This study was supported by research grants from the Institute of Health Carlos III (ISCIII) (PI18/00453, PI17/01104) and co-financed by the European Regional Development Fund (ERDF). BRM was supported by the 'Miguel Servet Type I' program (CP19/00098) from the ISCIII. FC was supported by the 'Nicolas Monardes' program from the Andalusian Health Public System (C-0032-2016). MQO was supported by the 'Miguel Servet Type II' program (CPII18/00003) from the ISCIII and by the 'Nicolas Monardes' program from the Andalusian Health Public System (C-0030-2018).

Subjects
Tejido adiposo, obesity, QH301-705.5, Obesidad, Adipose tissue, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid Sequence::Histone Code [Medical Subject Headings], Medicine (miscellaneous), H3k4me3, Resistencia a la insulina, Article, General Biochemistry, Genetics and Molecular Biology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance [Medical Subject Headings], Insulin resistance, insulin resistance, medicine, Obesity, Epigenetics, Biology (General), Gene, Anatomy::Cells::Cellular Structures::Extracellular Space::Extracellular Matrix [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Chromatin Immunoprecipitation [Medical Subject Headings], Código de histonas, biology, epigenetics, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [Medical Subject Headings], medicine.disease, Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings], Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Cell biology, adipose tissue, Histone, Epigenómica, biology.protein, H3K4me3, Chromatin immunoprecipitation, Extracellular matrix organization
Abstract

Background: Adipose tissue (AT) dysfunction is involved in obesity-related comorbidities. Epigenetic alterations have been recently associated with AT deterioration in obesity conditions. In this work, we profiled the H3K4me3 histone mark in human AT, with special emphasis on the changes in the pattern of histone modification in obesity and insulin resistance (IR). Visceral AT (VAT) was collected and subjected to chromatin immunoprecipitation (ChIP) using anti-H3K4me3 antibody and then sequenced to obtain the H3K4me3 genome profile. Results: We found that most of the H3K4me3 enriched regions were located in gene promoters of pathways related to AT biology and function. H3K4me3 enrichment at gene promoters was strongly related to higher mRNA levels. Differentially expressed genes in AT of patients classified as non-obese, obese with low IR, and obese with high IR could be regulated by differentially enriched H3K4me3, these genes encoded for pathways that could in part explain AT functioning during obesity and insulin resistance (e.g., extracellular matrix organization, PPARG signaling or inflammation). Conclusions: In conclusion, we emphasize the importance of the epigenetic mark H3K4me3 in VAT dysfunction in obesity and IR. The understanding of such mechanisms could give rise to the development of new epigenetic-based pharmacological strategies to ameliorate obesity-related comorbidities.

Published
2021
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12. Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges

Author

Kuchay, Mohammad Shafi, Martínez-Montoro, José Ignacio, Choudhary, Narendra Singh, Fernández-García, José Carlos, Ramos-Molina, Bruno, [Kuchay,MS] Division of Endocrinology and Diabetes, Medanta The Medicity Hospital, Gurugram, Haryana, India. [Martínez-Montoro,JI] Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain. [Choudhary,NS] Department of Hepatology, Medanta The Medicity Hospital, Gurugram, Haryana, India. [Fernández-García,JC] Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain. [Ramos-Molina,B] Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain., and This work was supported by the Institute of Health 'Carlos III' (ISCIII), co-funded by the 'Fondo Europeo de Desarrollo Regional-FEDER' (grant number PI20/00505). B.R.-M. was supported by the 'Miguel Servet Type I' program (CP19/00098, ISCIII, Spain, co-funded by the 'Fondo Europeo de Desarrollo Regional-FEDER).

Subjects
Síndrome metabólico, Microbioma gastrointestinal, nutritional and metabolic diseases, Insulin resistance, Gut microbiota, Chemicals and Drugs::Pharmaceutical Preparations [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Resistencia a la insulina, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings], Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings], digestive system, Metabolic syndrome, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Peroxisome Proliferator-Activated Receptors [Medical Subject Headings], digestive system diseases, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Adiposidad, Lean NAFLD, Visceral adiposity
Abstract

Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world's population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals. Yes

Published
2021

13. Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study

Author

Sandra Colorado, María José Sánchez, Ana Jimenez, Antonio Agudo, Pilar Amiano, Elena Salamanca-Fernández, Marcela Guevara, Nicolás Olea, Fernando Vela, Josu Delfrade, Juan P. Arrebola, Miguel Rodríguez-Barranco, Maria Dolores Chirlaque, [Salamanca-Fernández,E, Rodríguez-Barranco,M, Sánchez,MJ] Andalusian School of Public Health (EASP), Campus Universitario de Cartuja, Granada, Spain. [Salamanca-Fernández,E, Arrebola,JP, Vela,F, Olea,N, Sánchez,MJ] Instituto de Investigación Biosanitaria ibs. GRANADA, Granada, Spain. [Rodríguez-Barranco,M, Amiano,P, Delfrade,J, Chirlaque,MD, Colorado,S, Guevara,M, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P, Jimenez,A] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Delfrade,J, Guevara,M] Navarra Public Health Institute, Pamplona, Spain. [Delfrade,J, Guevara,M] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD, Colorado,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Sciences, University of Murcia, Murcia, Spain. [Colorado,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Arrebola,JP, Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Olea,N] Department of Radiology, University of Granada, Granada, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain., and This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016–06 AECC 'Junta provincial de Murcia'. FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain).

Subjects
Oncology, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings], Male, Neoplasias de la próstata, Health, Toxicology and Mutagenesis, Endocrine Disruptors, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Prostate cancer, Breast cancer, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Methacrylates::Bisphenol A-Glycidyl Methacrylate [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Factors de risc en les malalties, Hazard ratio, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Environmental pollutants, Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Bisphenol a, Endocrine disruptor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Neoplasias de la mama, Population study, Female, Public aspects of medicine, RA1-1270, Disruptores endocrinos, Adult, Risk, medicine.medical_specialty, endocrine system, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Risk factors in diseases, Population, Estudios de cohortes, Case-cohort, Check Tags::Male [Medical Subject Headings], Breast Neoplasms, Càncer de mama, Phenols, Bisfenol A glicidil metacrilato, Internal medicine, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Humans, Benzhydryl Compounds, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Càncer de pròstata, Proportional hazards model, business.industry, urogenital system, Research, Public Health, Environmental and Occupational Health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Endocrine Disruptors [Medical Subject Headings], Prostatic Neoplasms, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl Compounds [Medical Subject Headings], Environmental Exposure, medicine.disease, Industrial medicine. Industrial hygiene, RC963-969, Check Tags::Female [Medical Subject Headings], Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::Limit of Detection [Medical Subject Headings], business, Contaminantes ambientales
Abstract

This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016-06 AECC "Junta provincial de Murcia". FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain)., Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., Ministry of economy and competitiveness, National Institute of Health: Instituto de Salud Carlos III (ISCIII), AECC "Junta provincial de Murcia" PI14/00067- PI14/01716- PI14/01880- PI14/00556- BA15/00093- FFIS-CC 2016-06, Spanish Government RYC-2016-20155, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Catalan Institute of Oncology -ICO (Spain)

Published
2021

14. Molecular characterization and expression analysis of anti-Müllerian hormone in common carp (Cyprinus carpio) adult testes

Author

Angel A.A. Vigoya, Maira da Silva Rodrigues, Rafael Henrique Nóbrega, Juliana Ricci, Emanuel Ricardo Monteiro Martinez, Nuria E. Gómez-González, Amanda B. Stewart, Lucas B. Doretto, Arno Juliano Butzge, Marcos Antonio de Oliveira, Universidade Estadual Paulista (Unesp), San Martín University Foundation (FUSM), IMIB-Arrixaca, and West Virginia University

Subjects
Anti-Mullerian Hormone, Fish Proteins, Male, endocrine system, Carps, Mullerian Ducts, Common carp, Andrology, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Testis, Genetics, medicine, Animals, Carp, Spermatogenesis, Molecular Biology, Gametogenesis, 030304 developmental biology, 0303 health sciences, Sexual differentiation, biology, urogenital system, Ovary, Anti-Müllerian hormone, biology.organism_classification, Sertoli cell, medicine.anatomical_structure, anti-Müllerian hormone, biology.protein, Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Made available in DSpace on 2021-06-25T10:54:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Centers for Disease Control and Prevention Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação para o Desenvolvimento da UNESP (FUNDUNESP) Universidade Estadual Paulista ASCRS Research Foundation Anti-Müllerian hormone (Amh) is a member of the transforming growth factor-β (Tgf-β) superfamily required in the regression of Müllerian ducts during gonadal sex differentiation of higher vertebrates. Teleost fish lack Müllerian ducts, but identified Amh orthologs have been shown to exert crucial functions during sex determination and differentiation of several species of teleosts. However, the function of Amh during gametogenesis in adult fish remains poorly investigated. Therefore, to expand present knowledge on the role of Amh in teleosts, the present study aimed to isolate and clone full-length amh cDNA in the common carp, Cyprinus carpio, and examine its expression levels throughout the male reproductive cycle and in response to different hormone treatments of testicular explants. Molecular cloning and characterization showed that the common carp Amh precursor amino acid sequence shared common features to other fish Amh precursors, including a conserved C-terminus (Tgf-β domain) and a double proteolytic cleavage site (R-X-X-R-X-X-R) upstream to the Tgf-β domain. Expression analysis showed amh dimorphic expression in the adult gonads with higher expression in the testes than ovaries. In testes, amh mRNA was detected in Sertoli cells contacting different types of germ cells, although the expression was greatest in Sertoli cells associated with type A undifferentiated spermatogonia. Expression analysis during the reproductive cycle showed that amh transcripts were down-regulated during the developing phase, which is characterized by an increased proliferation of type A undifferentiated spermatogonia and Sertoli cells and appearance of spermatocytes (meiosis) in the testes. Furthermore, ex vivo experiments showed that a 7 day exposure to Fsh or estrogens was required to decrease amh mRNA levels in common carp testicular explants. In summary, this study provided information on the molecular characterization and transcript abundance of amh in common carp adult testes. Altogether, these data will be useful for further investigations on sex determination and differentiation in this species, and also to improved strategies for improved carp aquaculture, such as inhibiting precocious maturation of males. Aquaculture Program (CAUNESP) São Paulo State University (UNESP), Jaboticabal Reproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu Faculty of Veterinary Medicine and Animal Science San Martín University Foundation (FUSM) Department of Cell Biology and Histology Faculty of Biology Universidad de Murcia IMIB-Arrixaca Department of Orthopaedics Muscle skeletal Research West Virginia University Aquaculture Program (CAUNESP) São Paulo State University (UNESP), Jaboticabal Reproductive and Molecular Biology Group Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu

Published
2021

15. Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia

Author

Vicente Vicente, María Isabel Orts, Maria Luisa Lozano, Nuria Bermejo, María Perera, Estefanía Bolaños, Luis F. Casado-Montero, Gonzalo Carreño-Tarragona, Elisa Orna-Montero, Manuel A. Rodríguez-López, Isidro Jarque, Tomás José González-López, David Valcárcel, Maria Eva Mingot-Castellano, Aurora de Andrés, Silvana Novelli, Rosa M. Campos-Alvarez, María Fernanda López-Fernández, María Teresa Álvarez-Román, Nuria Revilla, José Ramón González-Porras, Institut Català de la Salut, [Lozano ML] Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CB15/00055-CIBERER, Murcia, Spain. [Mingot-Castellano ME] Hospital Carlos Haya, Málaga, Hospital Universitario Virgen del Rocio, Sevilla, Spain. [Perera MM] Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. [Jarque I] Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Campos-Alvarez RM] Hospital de Especialidades de Jerez de la Frontera, Cádiz, Spain. [González-López TJ] Hospital Universitario de Burgos, Burgos, Spain. [Valcarcel D] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, Hospital Universitari Vall d'Hebron, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, medicine.medical_treatment, lcsh:Medicine, Receptors, Fc, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Benzoates, chemistry.chemical_compound, 0302 clinical medicine, Trombocitopènia, hemic and lymphatic diseases, Young adult, lcsh:Science, Aged, 80 and over, Multidisciplinary, Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Coagulation Disorders::Purpura::Purpura, Thrombocytopenic::Purpura, Thrombocytopenic, Idiopathic [DISEASES], enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de la coagulación sanguínea::púrpura::púrpura trombocitopénica::púrpura trombocitopénica idiopática [ENFERMEDADES], Middle Aged, Prognosis, Survival Rate, Hydrazines, Thrombopoietin, 030220 oncology & carcinogenesis, Female, Receptors, Thrombopoietin, Haematological diseases, medicine.drug, Agonist, Adult, medicine.medical_specialty, medicine.drug_class, Recombinant Fusion Proteins, Splenectomy, Eltrombopag, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Author Correction, Survival rate, Immunological disorders, Aged, Retrospective Studies, Thrombopoietin receptor, Purpura, Thrombocytopenic, Idiopathic, Romiplostim, business.industry, lcsh:R, Retrospective cohort study, chemistry, Pyrazoles, lcsh:Q, Medicaments - Administració, business, 030215 immunology, Follow-Up Studies
Abstract

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

Published
2019

16. Physicians' and Nurses' Knowledge in Palliative Care: Multidimensional Regression Models

Author

Stella Martin-de-las-Heras, Leticia Rubio, Maria Dolores Medina-Abellan, Mónica López-García, Cristina M. Beltran-Aroca, María D. Pérez-Cárceles, Jaime Martin-Martin, [Martín-Martín,J, López-García,M, Martín-de-Las-Heras,S, and Rubio,L] Department of Human Anatomy and Legal Medicine, Instituto de Investigación Biomédica de Málaga (IBIMA), School of Medicine, University of Málaga, Málaga, Spain. [López-García,M] Fundación CUDECA, Benalmádena, Málaga, Spain. [Medina-Abellán,MD] Health Center in Espinardo, Health Service, Murcia, Spain. [Beltrán-Aroca,CM] Sección de Medicina Legal y Forense, Facultad de Medicina y Enfermería, Universidad de Córdoba, Córdoba, Spain. [Pérez-Cárceles,MD] Department of Legal and Forensic Medicine, School of Medicine, Biomedical Research Institute (IMIB-Arrixaca), University of Murcia, Murcia, Spain.

Subjects
knowledge, Health Knowledge, Attitudes, Practice, Palliative care, Cross-sectional study, Educación, Enfermeras y enfermeros, Health, Toxicology and Mutagenesis, legal medicine, Nurses knowledge, education, nurse, Nurses, Persons::Persons::Occupational Groups::Health Personnel::Physicians [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Palliative Care [Medical Subject Headings], Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, Health services, 0302 clinical medicine, Conocimiento, Nursing, Physicians, Surveys and Questionnaires, Medicine, Humans, 030212 general & internal medicine, Anthropology, Education, Sociology and Social Phenomena::Education::Educational Measurement::Professional Competence::Clinical Competence [Medical Subject Headings], Persons::Persons::Occupational Groups::Health Personnel::Nurses [Medical Subject Headings], Médicos, palliative care, physician, Health professionals, business.industry, Medicina forense, Public Health, Environmental and Occupational Health, Continuous training, Cuidados paliativos, Work experience, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Cross-Sectional Studies, 030220 oncology & carcinogenesis, Palliative Care Knowledge Test Spanish Version (PCKT-SV), Life expectancy, Clinical Competence, business
Abstract

The increase in life expectancy has led to a growth in the number of people in need of palliative care. Health professionals must possess appropriate knowledge and skills. This study aimed to assess knowledge in palliative care through the Palliative Care Knowledge Test Spanish Version (PCKT-SV)®. A cross-sectional analytical study was conducted in 40 primary care health services. A total of 600 PCKT-SV questionnaires were distributed among health professionals, 561 of them (226 nurses and 335 physicians) were properly filled up. Sociodemographic information, education, and work experience were also recorded. A total of 34.41% of the nurses and 67.40% of the physicians showed good or excellent knowledge of palliative care. Physicians’ scores for pain, dyspnea, and psychiatric disorders were higher than those of the nurses. Nurses scored significantly better in philosophy. Professionals with continuous training in palliative care showed a higher level of knowledge. Age and work experience of physicians and undergraduate training in nurses had significant weight in knowledge. Developing continuous training and enhancing undergraduate training in palliative care will lead to improved patient care at the end of life.

Published
2021

17. Dietary intake of trans fatty acids and breast cancer risk in 9 European countries

Author

Sahar Yammine, Agnès Fournier, Ann H. Rosendahl, Carlotta Sacerdote, Renée T. Fortner, Marco Lukic, Elisabete Weiderpass, Karina Standahl Olsen, Dagfinn Aune, Sandra Colorado-Yohar, J. Ramón Quirós, Valeria Pala, Eva Ardanaz, María José Sánchez, Christina C. Dahm, Antonio Agudo, Anne Tjønneland, Franziska Jannasch, Giovanna Masala, Laure Dossus, Veronique Chajes, Alicia K Heath, Anja Olsen, Signe Borgquist, Maria Wennberg, Carine Biessy, Marc J. Gunter, Salvatore Panico, Inger T. Gram, Neil Murphy, Pilar Amiano, Julie A. Schmidt, Rosario Tumino, Michèle Matta, Corinne Casagrande, Matthias B. Schulze, Inge Huybrechts, Bernard Srour, Centre international de Recherche sur le Cancer (CIRC), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), The Arctic University of Norway [Tromsø, Norway] (UiT), Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain] (IdiSNA), CIBER de Epidemiología y Salud Pública (CIBERESP), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), ibs.GRANADA Instituto de Investigación Biosanitaria [Granada, Spain], Universidad de Granada = University of Granada (UGR), Escuela Andaluza de Salud Pública [Granada, Spain] (EASP), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), German Institute of Human Nutrition Potsdam-Rehbruecke [Nuthetal, Germany] (GIHNP-R), Biodonostia Health Research Institute [Donostia-San Sebastian, Spain] (IIS Biodonostia), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Public Health Directorate [Asturias, Spain] (PHD), Provincial Health Authority (ASP 7) [Ragusa, Italy], Université de Naples, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], City of Health and Science University Hospital [Turin, Italy], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), University of Copenhagen = Københavns Universitet (UCPH), Aarhus University [Aarhus], Skane University Hospital [Lund], Umeå University, Imperial College London, Bjørknes University College [Oslo, Norvège], Oslo University Hospital [Oslo], University of Oxford, Malbec, Odile, The Arctic University of Norway (UiT), University of Granada [Granada], University of Copenhagen = Københavns Universitet (KU), and University of Oxford [Oxford]

Subjects
Industrial trans fatty acids, Conjugated linoleic acid, [SDV]Life Sciences [q-bio], Àcids grassos, Physiology, lcsh:Medicine, chemistry.chemical_compound, Eating, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, 2. Zero hunger, Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Hazard ratio, General Medicine, Trans Fatty Acids, Elaidic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Dieta, Female, Research Article, Risk, Ruminant trans fatty acids, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, General & Internal Medicine, Humans, Fatty acids, Proportional Hazards Models, Cancer och onkologi, business.industry, Proportional hazards model, lcsh:R, medicine.disease, Diet, chemistry, Cancer and Oncology, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Body mass index
Abstract

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk, MR/M012190/1 to EPIC-Oxford) (UK). We thank the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, and the National Institute for Public Health and the Environment (RIVM)-Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study., For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/ access/index.php., Informed consent was given by all study participants, and ethical approval for the entire EPIC cohort was obtained from the Institutional Review Board of the International Agency for Research on Cancer in Lyon, France, under protocol numbers SC/24/4 and SC/24/6, as well as from local ethics committees in the participating countries., The authors thank the EPIC participants and staff for their valuable contribution to this research and Bertrand Hemon (International Agency for Research on Cancer) for managing the data for the EPIC project., Background Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations., European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Deutsches Krebsforschungszentrum (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Catalan Institute of Oncology (Spain), Swedish Cancer Society Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C570/A16491 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, National Institute for Public Health and the Environment (RIVM)-Bilthoven, the Netherlands, Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), ERC-2009-AdG 232997

Published
2021

18. Surgical Application of Human Amniotic Membrane and Amnion-Chorion Membrane in the Oral Cavity and Efficacy Evaluation: Corollary With Ophthalmological and Wound Healing Experiences

Author

Stéphane Odet, Aurélien Louvrier, Christophe Meyer, Francisco J. Nicolas, Nicola Hofman, Brice Chatelain, Cédric Mauprivez, Sébastien Laurence, Halima Kerdjoudj, Narcisse Zwetyenga, Jean-Christophe Fricain, Xavier Lafarge, Fabienne Pouthier, Philippe Marchetti, Anne-Sophie Gauthier, Mathilde Fenelon, Florelle Gindraux, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Nanomédecine, imagerie, thérapeutique - UFC (EA 4662) (NIT / NANOMEDECINE), Université de Franche-Comté (UFC), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Biomatériaux et inflammation en site osseux - EA 4691 (BIOS), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Service Chirurgie Maxillo-Faciale - Stomatologie - Chirurgie Plastique Réparatrice et Esthétique - Chirurgie de la main (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service d'ophtalmologie [CHRU Besançon], Service de Chirurgie Orthopédique Traumatologique et Plastique [Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Nanomédecine, imagerie, thérapeutique - UFC (UR 4662) (NIT / NANOMEDECINE), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), and Colin, Marius

Subjects
0301 basic medicine, Histology, oral and maxillo-facial surgery, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Oral surgery, Biomedical Engineering, Dentistry, Bioengineering, wound healing, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Review, Hard tissue, Oral cavity, 03 medical and health sciences, 0302 clinical medicine, medicine, Oral mucosa, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Amnion, amniotic membrane, oral mucosa, business.industry, Bioengineering and Biotechnology, 030206 dentistry, 3. Good health, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, ophthalmology, 030104 developmental biology, medicine.anatomical_structure, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, business, Wound healing, Ocular surface, TP248.13-248.65, Biotechnology
Abstract

International audience; Due to its intrinsic properties, there has been growing interest in human amniotic membrane (hAM) in recent years particularly for the treatment of ocular surface disorders and for wound healing. Herein, we investigate the potential use of hAM and amnion-chorion membrane (ACM) in oral surgery. Based on our analysis of the literature, it appears that their applications are very poorly defined. There are two options: implantation or use as a cover material graft. The oral cavity is submitted to various mechanical and biological stimulations that impair membrane stability and maintenance. Thus, some devices have been combined with the graft to secure its positioning and protect it in this location. This current opinion paper addresses in detail suitable procedures for hAM and ACM utilization in soft and hard tissue reconstruction in the oral cavity. We address their implantation and/or use as a covering, storage format, application side, size and number, multilayer use or folding, suture or use of additional protective covers, re-application and resorption/fate. We gathered evidence on pre- and post-surgical care and evaluation tools. Finally, we integrated ophthalmological and wound healing practices into the collected information. This review aims to help practitioners and researchers better understand the application of hAM and ACM in the oral cavity, a place less easily accessible than ocular or cutaneous surfaces. Additionally, it could be a useful reference in the generation of new ideas for the development of innovative protective covering, suturing or handling devices in this specific indication. Finally, this overview could be considered as a position paper to guide investigators to fulfill all the identified criteria in the future.

Published
2021

19. Multiple Regionalized Genes and Their Putative Networks in the Interpeduncular Nucleus Suggest Complex Mechanisms of Neuron Development and Axon Guidance

Author

Isabel M. García-Guillén, Luis Puelles, Antonia Alonso, Faustino Marín, Pilar Aroca, and Department of Human Anatomy and Psychobiology, Faculty of Medicine, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia and IMIB-Arrixaca, Murcia, Spain

Subjects
0301 basic medicine, Interpeduncular nucleus, Neuroscience (miscellaneous), interactome, Biology, Interactome, interpeduncular nucleus, lcsh:RC321-571, lcsh:QM1-695, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, transcription factors, medicine, Gene family, Ephrin, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, rostral hindbrain, neuronal migration, Cell morphogenesis, axon guidance, Erythropoietin-producing hepatocellular (Eph) receptor, lcsh:Human anatomy, Brief Research Report, ephrin, Neuroanatomy, 030104 developmental biology, medicine.anatomical_structure, cadherin, Axon guidance, Neuron, Anatomy, Neuroscience, 5 - Ciencias puras y naturales [CDU], 030217 neurology & neurosurgery
Abstract

The interpeduncular nucleus (IPN) is a highly conserved limbic structure in the vertebrate brain, located in the isthmus and rhombomere 1. It is formed by various populations that migrate from different sites to the distinct domains within the IPN: the prodromal, rostral interpeduncular, and caudal interpeduncular nuclei. The aim here was to identify genes that are differentially expressed across these domains, characterizing their putative functional roles and interactions. To this end, we screened the 2,038 genes in the Allen Developing Mouse Brain Atlas database expressed at E18.5 and we identified 135 genes expressed within the IPN. The functional analysis of these genes highlighted an overrepresentation of gene families related to neuron development, cell morphogenesis and axon guidance. The interactome analysis within each IPN domain yielded specific networks that mainly involve members of the ephrin/Eph and Cadherin families, transcription factors and molecules related to synaptic neurotransmission. These results bring to light specific mechanisms that might participate in the formation, molecular regionalization, axon guidance and connectivity of the different IPN domains. This genoarchitectonic model of the IPN enables data on gene expression and interactions to be integrated and interpreted, providing a basis for the further study of the connectivity and function of this poorly understood nuclear complex under both normal and pathological conditions.

Published
2021

20. Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Author

Elena Arranz Canales, Elisenda Cortès-Saladelafont, Elena Martín-Hernández, Ricardo Gil Sánchez, Guillem Pintos-Morell, Javier Blasco-Alonso, Mónica A. López Rodríguez, David Moreno-Martinez, Encarna Guillén-Navarro, María Juliana Ballesta-Martínez, María Teresa García-Silva, María L. Couce, Pilar Quijada-Fraile, Montserrat Morales Conejo, Salvador García Morillo, Marc Moltó-Abad, Institut Català de la Salut, [Quijada-Fraile P, Martín-Hernández E] Unidad de Enfermedades Mitocondriales y Enfermedades Metabólicas Hereditarias, Servicio de Pediatría, Hospital Universitario 12 de Octubre, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), CIBERER, Madrid, Spain. [Arranz Canales E] Servicio de Medicina Interna, CSUR Enfermedades Metabólicas, MetabERN, Instituto de Investigación Sanitaria Hospital 12 de octubre (imas12), Hospital Universitario 12 de Octubre, Madrid, Spain. [Ballesta-Martínez MJ, Guillén-Navarro E] Sección de Genética Médica, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB Arrixaca, Universidad de Murcia, Murcia, Spain. CIBERER-ISCIII, Madrid, Spain. [Pintos-Morell G, Moltó-Abad M] Divisió de Malalties Minoritàries, Centre de Referència de Trastorns Metabòlics Hereditaris, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Moreno-Martínez D] Divisió de Malalties Minoritàries, Centre de Referència de Trastorns Metabòlics Hereditaris, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Lysosomal Storage Disorders Unit, The Royal Free Hospital NHS Foundation Trust and University College London, London, UK, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Adult, Ligamentous laxity, medicine.medical_specialty, Health-related quality of life, Mucopolysaccharidosis, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Hip dysplasia (canine), Young Adult, chemistry.chemical_compound, Elosulfase alfa, Quality of life, Interquartile range, Internal medicine, medicine, Hip Dislocation, Humans, Enzyme Replacement Therapy, Pharmacology (medical), Malalties rares - Tractament, Mucopolysaccharidosis IVA, Elosulfase alfa, Health-related quality of life, Mobility, Morquio A syndrome, Mucopolysaccharidosis IVA, terapéutica::farmacoterapia::terapia enzimática::tratamiento de sustitución enzimática [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Genetics (clinical), ambiente y salud pública::salud pública::medidas epidemiológicas::demografía::estado de salud::calidad de vida [ATENCIÓN DE SALUD], Mobility, business.industry, Research, Enzims - Ús terapèutic, Mucopolysaccharidosis IV, General Medicine, Enzyme replacement therapy, medicine.disease, Self Care, Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Health Status::Quality of Life [HEALTH CARE], Metabolisme, Errors congènits del - Tractament, enfermedades nutricionales y metabólicas::enfermedades metabólicas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::mucopolisacaridosis::enfermedades nutricionales y metabólicas::enfermedades metabólicas::alteraciones congénitas del metabolismo::mucopolisacaridosis IV [ENFERMEDADES], chemistry, Dysplasia, Quality of Life, Medicine, Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Mucopolysaccharidoses::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolism, Inborn Errors::Mucopolysaccharidosis IV [DISEASES], sense organs, business, Morquio A syndrome, Therapeutics::Drug Therapy::Enzyme Therapy::Enzyme Replacement Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract

Background Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams.

Published
2021

21. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

Author

María Cortés-Rodríguez, Norma C. Gutiérrez, Juan J. Lahuerta, María del Carmen Couto, Enrique M. Ocio, Jose M Arguiñano, Jesús F. San-Miguel, María José Casanova, Jesús Martín, M. Teresa Cedena, Javier de la Rubia, Maria Luisa Martin, Ana Isabel Teruel, Esther González, Bruno Paiva, Ernesto Pérez-Persona, Verónica González-Calle, Laura Rosiñol, María José Calasanz, Cristina Encinas, Rafael Rios, Morton Coleman, Ruben Niesvizky, Miguel T. Hernandez, Ana M. Vale, Maria-Victoria Mateos, Adrian Alegre, Mercedes Gironella, Noemi Puig, Sebastián Garzón, Ricarda García-Sánchez, Felipe de Arriba, Guillermo Martín-Sánchez, Joan Bladé, Mario Arnao, Marta González, Fernando Escalante, Albert Oriol, Universidad de Cantabria, Institut Català de la Salut, [Puig N] Hematology Department, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain. [Hernández MT] Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain. [Rosiñol L] Hematology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain. [González E] Hospital Universitario de Cabueñes, Gijón, Spain. [de Arriba F] Hospital Morales Meseguer, IMIB-Arrixaca, Universidad de Murcia, Murcia, Spain. [Oriol A] Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain. [Gironella M] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Surgical Procedures, Operative::Transplantation::Transplantation, Autologous [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Myeloma, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Gastroenterology, THERAPY, Dexamethasone, law.invention, Randomized controlled trial, law, Clarithromycin, Antineoplastic Combined Chemotherapy Protocols, terapéutica::farmacoterapia::farmacoterapia combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Clinical endpoint, Lenalidomide, Multiple myeloma, RC254-282, Aged, 80 and over, POMALIDOMIDE, Therapeutics::Drug Therapy::Drug Therapy, Combination [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Hematopoietic Stem Cell Transplantation, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma [DISEASES], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Hematology, Treatment Outcome, Oncology, BIRD, BIAXIN, Randomized controlled trials, Female, Multiple Myeloma, medicine.drug, Mieloma múltiple - Tractament, medicine.medical_specialty, LOW-DOSE DEXAMETHASONE, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Neutropenia, Transplantation, Autologous, Article, Internal medicine, medicine, neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple [ENFERMEDADES], Humans, Adverse effect, COMBINATION, intervenciones quirúrgicas::trasplante::trasplante autólogo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Aged, business.industry, Teràpia cel·lular, medicine.disease, business
Abstract

© The Author(s) 2021., Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.

Published
2021

22. Reductions in blood concentrations of persistent organic pollutants in the general population of Barcelona from 2006 to 2016

Author

Porta, M., Pumarega, José Antonio, Henríquez-Hernández, L.A., Gasull, Magda, Bartoll, Xavier, Arrebola, J.P., Morales, E., Ibarluzea, Jesús, Alguacil, Juan, Bilal, Usama, Luzardo, O.P., Universitat Autònoma de Barcelona, [Porta, Miquel] Hosp del Mar Med Res Inst IMIM, Barcelona, Spain, [Pumarega, Jose] Hosp del Mar Med Res Inst IMIM, Barcelona, Spain, [Gasull, Magda] Hosp del Mar Med Res Inst IMIM, Barcelona, Spain, [Porta, Miquel] Univ Autonoma Barcelona, Sch Med, Barcelona, Spain, [Pumarega, Jose] Univ Autonoma Barcelona, Sch Med, Barcelona, Spain, [Gasull, Magda] Univ Autonoma Barcelona, Sch Med, Barcelona, Spain, [Porta, Miquel] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Pumarega, Jose] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Gasull, Magda] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Arrebola, Juan P.] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Morales, Eva] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Ibarluzea, Jesus] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Alguacil, Juan] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain, [Henriquez-Hernandez, Luis A.] Univ Las Palmas Gran Canaria, Res Inst Biomed & Hlth Sci IUIBS, Dept Clin Sci, Toxicol Unit, Canary Isl, Spain, [Luzardo, Octavio P.] Univ Las Palmas Gran Canaria, Res Inst Biomed & Hlth Sci IUIBS, Dept Clin Sci, Toxicol Unit, Canary Isl, Spain, [Henriquez-Hernandez, Luis A.] CIBER Obesidad & Nutr CIBEROBN, Madrid, Spain, [Luzardo, Octavio P.] CIBER Obesidad & Nutr CIBEROBN, Madrid, Spain, [Bartoll, Xavier] Agencia Salut Publ Barcelona, Barcelona, Spain, [Arrebola, Juan P.] Inst Invest Biosanitaria Ibs Granada, Granada, Spain, [Arrebola, Juan P.] Univ Granada, Dept Prevent Med & Publ Hlth, Granada, Spain, [Morales, Eva] Univ Murcia, Dept Publ Hlth Sci, IMIB Arrixaca, Murcia, Spain, [Ibarluzea, Jesus] Basque Govt, Subdirectorate Publ Hlth & Addict Gipuzkoa, San Sebastian, Spain, [Ibarluzea, Jesus] Univ Basque Country, Fac Psychol, San Sebastian, Spain, [Ibarluzea, Jesus] Biodonostia Hlth Res Inst, Environm Epidemiol & Child Dev Grp, San Sebastian, Spain, [Alguacil, Juan] Univ Huelva, Huelva, Spain, [Bilal, Usama] Drexel Dornsife Sch Publ Hlth, Urban Hlth Collaborat, Philadelphia, PA USA, [Bilal, Usama] Drexel Univ, Dornsife Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA, Instituto de Salud Carlos III, Ministry of Health, Government of Spain - FEDER, Instituto de Salud Carlos III, Ministry of Health, Government of Spain - FEDER (CIBER de Epidemiologia y Salud Publica CIBERESP), Hospital del Mar Medical Research Institute (IMIM) , Barcelona, Government of Catalonia, Fundacio La Marato de TV3, CRUE-Santander Fondo Supera Covid19, and Office of the Director of the National Institutes of Health

Subjects
Risk, Environmental Engineering, 010504 meteorology & atmospheric sciences, Polybrominated diphenyl ethers (PBDEs), Disrupting chemicals, Population, Serum-levels, 010501 environmental sciences, Representative sample, 01 natural sciences, Exposure, Environmental exposure/human samples, Pops, Polybrominated diphenyl ethers (PDBEs), Environmental health, Environmental Chemistry, Medicine, Polycyclic aromatic-hydrocarbons, Persistent organic pollutants (POPs), education, Waste Management and Disposal, 0105 earth and related environmental sciences, Pollutant, education.field_of_study, Pesticide residues, business.industry, Serum concentration, medicine.disease, Environmental exposure, Health survey, Pollution, Obesity, Environmental pollutants, Human biomonitoring, Policy, Normal weight, Health, Polycyclic aromatic hydrocarbons (PAHs), Organochlorine pesticides, Physical exam, business, human samples
Abstract

The work was supported in part by research grants from Instituto de Salud Carlos III, Ministry of Health, Government of Spain - cofunded by FEDER (FIS PI13/00020, FIS PI17/00088, and CIBER de Epidemiologia y Salud Publica CIBERESP) ; the Hospital del Mar Medical Research Institute (IMIM) , Barcelona; the Government of Catalonia (2014 SGR 1012, 2017 SGR 439) ; Fundacio La Marato de TV3 (20132910) ; and the CRUE-Santander Fondo Supera Covid19 (15072020) . UB was supported by the Office of the Director of the National Institutes of Health under award number DP5OD26429. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Background: Few cities in the world biomonitor changes in human levels of persistent organic pollutants (POPs) through periodic health surveys representative of the general population. Objectives: To analyze changes in serum concentrations of POPs in Barcelona from 2006 to 2016, and to analyze socio-demographic correlates of concentrations of 62 POPs in 2016. Methods: Participants in the Barcelona Health Surveys of 2006 and 2016 (N = 231 and 240, respectively) were interviewed face-to-face, gave blood, and underwent a physical exam. POPs were analyzed by gas chromatography mass spectrometry. Results: Concentrations of all nine most prevalent compounds decreased markedly during the 10-years . Reductions occurred in almost all sex, age and BMI subgroups. For most organochlorine compounds the reduction was larger in women than men (for HCB, & minus;77% and & minus; 62%, respectively). For beta-HCH, PCBs, naphthalene and phenanthrene the decrease was larger in the younger groups. Large reductions in concentrations of PCBs and DDE were observed in individuals with normal weight but not in individuals with obesity. Conclusions: While concentrations of most POPs are decreasing in Barcelona, significant sociodemographic differences in such reductions warrant strengthening public and private policies towards groups making slower progress. A relevant component of the success in the current decreasing is a reduction of differences (convergence) by gender., Instituto de Salud Carlos III, Ministry of Health, Government of Spain - FEDER FIS PI13/00020 FIS PI17/00088, Instituto de Salud Carlos III, Ministry of Health, Government of Spain - FEDER (CIBER de Epidemiologia y Salud Publica CIBERESP), Hospital del Mar Medical Research Institute (IMIM) , Barcelona, Generalitat de Catalunya 2014 SGR 1012 2017 SGR 439, Fundacio La Marato de TV3 20132910, CRUE-Santander Fondo Supera Covid19 15072020, United States Department of Health & Human Services National Institutes of Health (NIH) - USA DP5OD26429

Published
2021

23. Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain)

Author

Leire Gil-Majuelo, Tania Fernández-Villa, Nuria Aragonés, Pilar Amiano, Esther Gracia-Lavedan, Juan Alguacil, Inmaculada Salcedo-Bellido, A. Delgado-parrilla, Cristina O'Callaghan-Gordo, Virginia Lope, Maria Dolores Chirlaque, Marta Maria Rodriguez-Suarez, Rafael Marcos-Gragera, Marcela Guevara, Dolores Salas, Rosana Peiró-Pérez, Inés Gómez-Acebo, Gemma Castaño-Vinyals, Marina Pollán, Trinidad Dierssen-Sotos, M. Pinto-carbó, Manolis Kogevinas, Antonio J. Molina, Conchi Moreno-Iribas, Mercedes Vanaclocha-Espi, Beatriz Pérez-Gómez, Mireia Obón-Santacana, Ana Molina-Barceló, Universidad de Cantabria, Universitat Oberta de Catalunya (UOC), Universidad de Granada, Universidad de Huelva, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBEResp), Instituto de Salud Carlos III, European Regional Development Fund, Fundación Marqués de Valdecilla, International Cancer Genome Consortium, Ministerio de Economía y Competitividad (España), Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de Murcia, Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), [Pinto-Carbo,M, Molina-Barcelo,A, Vanaclocha-Espi,M, Salas,D] Cancer and Public Health Area, Foundation for the Promotion of the Research in Healthcare and Biomedicine (FISABIO-Salud Pública), Valencia, Valencian Community, Spain. [Peiró-Pérez,R] Inequalities Area, Foundation for the Promotion of the Research in Healthcare and Biomedicine (FISABIO-Salud Pública), Valencia, Valencian Community, Spain. [Peiró-Pérez,R, Salas,D] General Directorate of Public Health, Valencia, Valencian Community, Spain. [Peiró-Pérez,R, Alguacil,J, Castaño-Vinyals,G, O’Callaghan-Gordo,C, Gràcia-Lavedan,E, Pérez-Gómez,B, Lope,V, Aragonés,N, Amiano,P, Dierssen-Soto,T, Gómez-Acebo,I, Guevara,M, Obón-Santacana,M, Salcedo-Bellido,I, Marcos-Gragera,R, Chirlaque,MD, Kogevinas,M, Pollán,M, Salas,D] Consortium for Biomedical Research in Epidemiology and Public Health (CIBEResp), Madrid, Spain. [Alguacil,J, Delgado-Parrilla,A] Centre for Health and Environmental Research, Huelva University, Huelva, Andalucia, Spain. [Castaño-Vinyals,G, Kogevinas,M] Barcelona Institute for Global Health (ISGlobal), Barcelona, Catalonia, Spain. [Castaño-Vinyals,G, O’Callaghan-Gordo,G, Kogevinas,M] Universitat Pompeu Fabra, Plaça de la Mercè, Barcelona, Catalonia, Spain. [Castaño-Vinyals,G, Kogevinas,M] Hospital del Mar Medical Research Institute, Barcelona, Catalonia, Spain. [O’Callaghan-Gordo,C] Faculty of Health Science,Universitat Oberta de Catalunya, Barcelona, Catalonia, Spain. [Pérez-Gómez,B, Pollán,M] Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Aragonés,N] Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain. [Molina,AJ, Fernández-Villa,T] The Research Group in Gene—Environment and Health Interactions, Institute of Biomedicine (IBIOMED), University of León, León, Castilla y León, Spain. [Gil-Majuelo,L, Amiano,P] Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Gipuzkoa, Spain. [Gil-Majuelo,L, Amiano,P] Biodonostia Health Research Institute, Group of Epidemiology of Chronic and Communicable Diseases, San Sebastián, Gipuzkoa, Spain. [Dierssen-Sotos,T, Gómez-Acebo,I] Cantabria University, Santander, Cantabria, Spain. [Guevara,M, Moreno-Iribas,C] Navarra Public Health Institute, Pamplona, Navarra, Spain. [Guevara,M, Moreno-Iribas,C] Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain. [Obón-Santacana,M] Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Barcelona, Catalonia, Spain. [Obón-Santacana,M] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain. [Rodríguez-Suárez,MM] Preventive Medicine and Public Health Area, Oviedo University, Oviedo, Asturias, Spain. [Rodríguez-Suárez,MM] Central University Hospital of Asturias, Public Health Service of the Principe de Asturias, Oviedo, Asturias, Spain. [Salcedo-Bellido,I] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Andalucia, Spain. [Salcedo-Bellido,I] Departamento de Medicina Preventiva y Salud Publica, Universidad de Granada, Granada, Andalucia, Spain. [Marcos-Gragera,R] Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Department of Health, Autonomous Government of Catalonia, Catalan Institute of Oncology, Girona, Catalonia, Spain. [Marcos-Gragera,R] Descriptive Epidemiology, Genetics and Cancer Prevention Group [Girona Biomedical Research Institute], Girona, Catalonia, Spain. [Chirlaque,D] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, El Palmar, Murcia, Spain., and This research was supported by the 'Acción Transversal del Cancer', approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo.

Subjects
Male, Behavioral and social aspects of health, Health Behavior, España, Social Sciences, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Tobacco Use::Smoking [Medical Subject Headings], Gender perspective, healthy behaviours, Hàbits sanitaris, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Movilidad social, Sociology, Social mobility, Medicine and Health Sciences, Socioeconomic aspects of health, Public and Occupational Health, European commission, Alcohol consumption, Salut, 030212 general & internal medicine, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Social Class [Medical Subject Headings], Perspectiva de género, Aged, 80 and over, Multidisciplinary, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors [Medical Subject Headings], multicase-control study, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior [Medical Subject Headings], Middle Aged, Sexual and gender issues, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Social Class::Social Mobility [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Health, language, Medicine, Female, 0305 other medical science, Persons::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Research Article, Adult, Science, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Healthy lifestyle, Clase social, Check Tags::Male [Medical Subject Headings], Genre studies, Education, socioeconomic status, 03 medical and health sciences, Young Adult, Sex Factors, Political science, Cancer genome, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Socioeconomic Factors [Medical Subject Headings], Humans, social mobility, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Health behavior, Exercise, Educational Attainment, Nutrition, Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], 030505 public health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys [Medical Subject Headings], Physical activity, Biology and Life Sciences, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Health Surveys, language.human_language, Diet, Health Care, Check Tags::Female [Medical Subject Headings], Social Class, Socioeconomic Factors, Estudis de gènere, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Spain, Case-Control Studies, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Catalan, Gender studies, Estilo de vida saludable, Humanities
Abstract

This research was supported by the “Acción Transversal del Cancer”, approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008–2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged, “Acción Transversal del Cancer” by the Spanish Council of Ministers, Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092, Fundación Marqués de Valdecilla [grant number: API 10/09], ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], Junta de Castilla y León [grant number: LE22A10-2], Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], Recercaixa [grant number: 2010ACUP00310], Regional Government of the Basque Country, Consejería de Sanidad de la Región de Murcia, European Commission [grant number: FOOD-CT-2006-036224-HIWATE], Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE, Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], Fundación Caja de Ahorros de Asturias, University of Oviedo

Published
2021

24. A decade of changes in management of immune thrombocytopenia, with special focus on elderly patients

Author

José Ramón González-Porras, Aurora de Andrés, Maria Luisa Lozano, Vicente Vicente, María Perera, Elisa Orna-Montero, Isidro Jarque, María Isabel Orts, Nuria Bermejo, Rosa M. Campos-Alvarez, Gonzalo Carreño-Tarragona, Tomás José González-López, Estefanía Bolaños, David Valcárcel, Luis F. Casado-Montero, María Fernanda López-Fernández, Elsa López-Ansoar, María Teresa Álvarez-Román, Maria Eva Mingot-Castellano, Silvana Novelli, Institut Català de la Salut, [Lozano ML] Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CB15/00055-CIBERER, Murcia, Spain. [Mingot-Castellano ME] Hospital Carlos Haya, Málaga, Hospital Universitario Virgen del Rocio, Sevilla, Spain. [Perera MM] Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain. [Jarque I] Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Campos-Alvarez RM] Hospital de Especialidades de Jerez de la Frontera, Cádiz, Spain. [González-López TJ] Hospital Universitario de Burgos, Burgos, Spain. [Valcarcel D] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and Amgen

Subjects
0301 basic medicine, Male, Pediatrics, enfermedades del sistema inmune::enfermedades del sistema inmune::púrpura trombocitopénica::púrpura trombocitopénica idiopática [ENFERMEDADES], medicine.medical_treatment, Persones grans, 0302 clinical medicine, Second line, Elderly, immune system diseases, hemic and lymphatic diseases, Aged, 80 and over, Trombocitopènia - Tractament, Other subheadings::Other subheadings::/agonists [Other subheadings], Age Factors, food and beverages, Disease Management, hemic and immune systems, Hematology, Middle Aged, Immune System Diseases::Autoimmune Diseases::Immune System Diseases::Purpura, Thrombocytopenic, Idiopathic [DISEASES], Treatment Outcome, Persons::Age Groups::Adult::Aged [NAMED GROUPS], embryonic structures, Otros calificadores::Otros calificadores::/agonistas [Otros calificadores], Citocines - Receptors, Molecular Medicine, Female, Receptors, Thrombopoietin, Adult, medicine.medical_specialty, Thrombopoietin Receptor Agonists, Splenectomy, TPO-RA, Guidelines, aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de citocinas::receptores de trombopoyetina [COMPUESTOS QUÍMICOS Y DROGAS], 03 medical and health sciences, Young Adult, medicine, Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Thrombopoietin [CHEMICALS AND DRUGS], Humans, Molecular Biology, personas::Grupos de Edad::adulto::anciano [DENOMINACIONES DE GRUPOS], Aged, Retrospective Studies, Purpura, Thrombocytopenic, Idiopathic, Adult patients, business.industry, Cell Biology, Immune thrombocytopenia, 030104 developmental biology, ITP, business, 030215 immunology
Abstract

[Background]: Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze the implementation of current recommendations in the standard practice of adult ITP patients, and how age may influence those changes., [Methods]: We included 121 adult patients (> 65 years, n = 54; younger individuals, n = 67) who initiated treatment with TPO-RA between January 2012 and December 2014., [Results]: Patients older than 65 years treated with TPO-RA presented at diagnosis with significantly higher platelet counts, less bleeding, and a more prothrombotic profile than younger ones. The high efficacy rates of TPO-RA, preferentially used during the last decade in non-chronic phases, precluded from further therapies in the majority of ITP patients. Their administration was associated with a sharp decline in the last decade in the use of splenectomy and intravenous immunoglobulin, especially in younger ITP individuals., [Conclusion]: These results confirm (1) that there is a preferential use of TPO-RAs in elderly ITP patients with fewer bleeding complications but more unfavorable prothrombotic conditions than in younger individuals, and (2) that early use of these agents has been established as an effective therapeutic alternative to other second line therapies., This work was supported by Amgen S.A. Spain.

Published
2020

25. Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

Author

Rafael Ordóñez, Jaime Gómez-Millán, José Antonio Medina, Isaac Plaza-Andrade, Lidia Sánchez-Alcoholado, Bruno Ramos-Molina, María Isabel Queipo-Ortuño, Ana Otero, Aurora Laborda-Illanes, [Sánchez-Alcoholado,L, Plaza-Andrade,I, Laborda-Illanes,A, Queipo-Ortuño,MI] Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, Málaga, Spain. [Sánchez-Alcoholado,L, Laborda-Illanes,A] Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Ordóñez,R, Otero,A, Medina,JA, Gómez-Millán,J] Unidad de Gestión Clínica de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Ramos-Molina,B] Grupo de Cirugía Digestiva, Endocrina y Transplante de Órganos Abdominales, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain., This work was supported by PI15/00256 from the Institute of Health 'Carlos III' (ISCIII), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Maria Isabel Queipo-Ortuño was supported by the 'Miguel Servet Type II' program (CPI13/00003, ISCIII, Spain, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER), and by the 'Nicolas Monardes' research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Bruno Ramos Molina was supported by the 'Miguel Servet Type I' program (CP19/00098, ISCIII, Spain, and co-funded by the Fondo Europeo de Desarrollo Regional-FEDER). Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain). Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain.

Subjects
Male, 0301 basic medicine, obesity, Diseases::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Colorectal cancer, Obesidad, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins [Medical Subject Headings], Gut flora, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::Obesity [Medical Subject Headings], Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], lcsh:Chemistry, Feces, 0302 clinical medicine, Neoplasias colorrectales, lcsh:QH301-705.5, Spectroscopy, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], biology, General Medicine, Middle Aged, Computer Science Applications, 030220 oncology & carcinogenesis, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Precursors [Medical Subject Headings], Female, gut permeability, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis [Medical Subject Headings], Inflammation Mediators, medicine.symptom, Colorectal Neoplasms, Microbioma gastrointestinal, Anatomy::Fluids and Secretions::Feces [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Inflammation, Context (language use), colorectal cancer, TMAO, digestive system, Permeability, Article, Catalysis, Proinflammatory cytokine, Inorganic Chemistry, Methylamines, 03 medical and health sciences, medicine, Humans, Protein Precursors, Physical and Theoretical Chemistry, Molecular Biology, neoplasms, Organisms::Bacteria [Medical Subject Headings], Aged, Intestinal permeability, Inflamación, Chemicals and Drugs::Organic Chemicals::Amines::Methylamines [Medical Subject Headings], Bacteria, Haptoglobins, gut microbiota, business.industry, Interleukins, Organic Chemistry, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], biology.organism_classification, medicine.disease, Phenomena and Processes::Chemical Phenomena::Permeability [Medical Subject Headings], Health Care::Environment and Public Health::Public Health::Epidemiologic Measurements::Biometry::Anthropometry::Body Mass Index [Medical Subject Headings], digestive system diseases, Gastrointestinal Microbiome, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], lcsh:Biology (General), lcsh:QD1-999, inflammation, Immunology, Dysbiosis, Metagenome, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Acute-Phase Proteins::Haptoglobins [Medical Subject Headings], business, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings], Biomarkers, Chemicals and Drugs::Biological Factors::Inflammation Mediators [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Metagenome [Medical Subject Headings]
Abstract

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1&beta, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Published
2020

26. The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Author

Sánchez-Alcoholado, Lidia, Ramos-Molina, Bruno, Otero, Ana, Laborda-Illanes, Aurora, Ordóñez, Rafael, Medina, José Antonio, Gómez-Millán, Jaime, Queipo-Ortuño, María Isabel, [Sánchez-Alcoholado,L, Laborda-Illanes,A, Queipo-Ortuño,MI] Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria. Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, Málaga, Spain. [Ramos-Molina,B] Departamento de Cirugía Digestiva, Endocrina y Transplante de Órganos Abdominales, Instituto Murciano de Investigación Biosanitária (IMIB-Arrixaca), Murcia, Spain. [Otero,A, Ordóñez,R, Medina,JA, Gómez-Millán,J] Unidad de Gestión Clínica de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria. Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain., This work was supported by PI15/00256 from the Institute of Health 'Carlos III' (ISCIII), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Maria Isabel Queipo-Ortuño was supported by the 'Miguel Servet Type II' program (CPI13/00003, ISCIII, Spain, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER), and by the 'Nicolas Monardes' research program of the Consejería de Salud (C-0030-2018, Junta de Andalucía, Spain. Bruno Ramos Molina was supported by a 'Miguel Servet Type I' program (CP19/00098, ISCIII, Spain, and co-funded by the Fondo Europeo de Desarrollo Regional-FEDER). Lidia Sanchez-Alcoholado was recipient of a predoctoral grant (PE-0106-2019) from the Consejería de Salud y Familia (co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Andalucia, Spain). Aurora Laborda-Illanes was recipient of a predoctoral grant PFIS-ISCIII (FI19-00112) co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, Madrid, Spain.

Subjects
Polifenoles, Microbioma gastrointestinal, Technology and Food and Beverages::Food and Beverages::Food::Dietary Supplements::Probiotics [Medical Subject Headings], Disbiosis, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Polyphenols [Medical Subject Headings], Gut microbiota, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Short-chain fatty acids, Ácidos grasos insaturados, Neoplasias colorrectales, Chemicals and Drugs::Organic Chemicals::Amines::Polyamines [Medical Subject Headings], Polyamines, Poliaminas, Fibras de la dieta, Technology and Food and Beverages::Food and Beverages::Food::Dietary Fiber [Medical Subject Headings], Organisms::Bacteria [Medical Subject Headings], Inflammation, Inflamación, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Volatile [Medical Subject Headings], Probiotics, Ácidos grasos volátiles, Probióticos, Polyphenols, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Colorectal cancer, Dietary fiber, Dysbiosis, Polyunsaturated fatty acids, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Dysbiosis [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated [Medical Subject Headings]
Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy. Yes

Published
2020

27. 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

28. Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain

Author

Nuria Aragonés, Facundo Vitelli-Storelli, Inés Gómez-Acebo, Gemma Castaño-Vinyals, Eva Adarnaz, Marina Pollán, Raul Zamora-Ros, Juan Alguacil, Estefanía Toledo, Manolis Kogevinas, Antonio J. Molina, José Juan Jiménez-Moleón, Vicente Martín, Ana Molina-Barceló, María Rubín-García, Guillermo Fernández-Tardón, María Dolores Chirlaque, Beatriz Pérez-Gómez, Mireia Obón-Santacana, Instituto de Salud Carlos III, Fundación Marqués de Valdecilla, Ministerio de Economía y Competitividad (España), Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de la Región de Murcia (España), Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), Ministerio de Educación (España), University of Leon (España), Ministerio de Ciencia e Innovación (España), Junta de Castilla y León, Gobierno de Andalucía, Generalitat Valenciana, Recercaixa, Gobierno Vasco, Gobierno de Murcia, European Commission, Fundación Científica AECC, Generalitat de Catalunya, Universidad de Oviedo, Universidad de León, Universidad de Cantabria, [Rubín-García,M, Vitelli-Storelli,F, Molina,AJ, Martín,V] Group of Investigation in Interactions Gene-Environment and Health (GIIGAS), Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Zamora-Ros,R] Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet del Llobregat, Barcelona, Spain. [Aragonés,N] Department of Health of Madrid, Epidemiology Section, Public Health Division, Madrid, Spain. [Aragonés,N, Adarnaz,E, Castaño-Vinyals,G, Gómez-Acebo,I, Fernández-Tardón,G, Jiménez-Moleón,JJ, Alguacil,J, Dolores Chirlaque,MD, Pérez-Gómez,B, Pollán,M, Kogevinas,M, Martín,V] Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Adarnaz,E, Toledo,E] Institute for Health Research (IdiSNA), Pamplona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Department of Public Health, Universitat Pompeu Fabra (UPF), Campus del Mar, Barcelona, Spain. [Obón-Santacana,M] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet De Llobregat, Barcelona, Spain. [Obón-Santacana,M] Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet Del Llobregat, Barcelona, Spain. [Gómez-Acebo,I] Facultad de Medicina, Universidad de Cantabria, IDIVAL, Santander, Spain. [Molina-Barceló,A] Cancer and Public Health Area, FISABIO-Public Health, Valencia, Spain. [Fernández-Tardón,G] Health Research Institute of the Principality of Asturias (ISPA), Oncology Institute, University of Oviedo, Oviedo, Asturias. [Jiménez-Moleón,JJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Hospitales Universitarios de Granada, Universidad de Granada, Granada, Spain. [Alguacil,J] Centro de Investigación en Recursos Naturales, Salud y Medio Ambiente (RENSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Campus de Ciencias de la Salud, El Palmar, Murcia, Spain. [Toledo,E] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. [Toledo,E] Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain. [Pérez-Gómez,B, Pollán,M] Cancer and Environmental Epidemiology Unit, Department of Epidemiology and Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Pérez-Gómez,B] Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro, IDIPHIM, Madrid, Spain., and The study was partially funded by the 'Accion Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. IDIBELL is a member of the CERCA Programme, Generalitat de Catalunya. R.Z.-R. was supported by the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (Co-funded by the European Social Fund (ESF)-ESF investing in your future). M.R.-G., is supported by the Ministry of Education of Spain (FPU17/06488) and by University of León. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program.

Subjects
0301 basic medicine, Male, stilbenes, Logistic regression, Gastroenterology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Eating, 0302 clinical medicine, Estilbenos, Risk Factors, Epidemiology, histologic, Odds Ratio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Prospective cohort study, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrition and Dietetics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Stomach, lignans, MCC-Spain, Middle Aged, anatomic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Quartile, 030220 oncology & carcinogenesis, Dieta, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, epidemiology, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzyl Compounds::Lignans [Medical Subject Headings], lcsh:Nutrition. Foods and food supply, medicine.medical_specialty, Neoplasias gástricas, Polifenoles, Stomach cancer, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Polyphenols [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Anatomy::Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Stomach [Medical Subject Headings], lcsh:TX341-641, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diet Surveys, Article, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Epidemiología, Humans, Compuestos fenólicos, Epidemiologia, Nutrició, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutrition Processes::Eating [Medical Subject Headings], polyphenols, Nutrition, Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms [Medical Subject Headings], Càncer d'estómac, gastric cancer, Cancer, Lignanos, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, Phenolic acid, medicine.disease, Diet, 030104 developmental biology, Logistic Models, Check Tags::Female [Medical Subject Headings], chemistry, Polyphenol, Spain, Case-Control Studies, business, diet, phenolic acids, Food Science
Abstract

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from di erent regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed e ects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No di erences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results., Instituto de Salud Carlos III, Instituto de Salud Carlos III European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773-Cantabria PS09/01286-Leon PS09/01903-Valencia PS09/02078-Huelva PS09/01662-Granada PI11/01403 PI11/01889-FEDER PI11/00226 PI11/01810 PI11/02213 PI12/00488, Instituto de Salud Carlos III API 10/09, ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through Red Tematica de Investigacion del Cancer (RTICC) del ISCIII) RD12/0036/0036, Junta de Castilla y León LE22A10-2, Junta de Andalucía PI-0571-200 PI-0306-2011 salud201200057018tra, Conselleria de Sanitat of the Generalitat Valenciana AP_061/10, La Caixa Foundation 2010ACUP 00310, Regional Government of the Basque Country, Consejería de Sanidad de la Región de Murcia, European Commission European Commission Joint Research Centre FOOD-CT-2006-036224-HIWATE, Spanish Association Against Cancer (AECC) Scientific Foundation, Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 2014SGR850, Fundación Caja de Ahorros de Asturias, University of Oviedo, "Miguel Servet" program from the Institute of Health Carlos III (European Social Fund (ESF)-ESF investing in your future) CP15/00100, Ministry of Education of Spain FPU17/06488, University of Leon, Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program CEX2018-000806-S, Generalitat de Catalunya through the CERCA Program, The Instituto de Salud Carlos III-FEDER PI12/00265 PI12/01270 PI12/00715 PI12/00150 PI14/01219 PI14/0613 PI15/00069 PI15/00914 PI15/01032 PI17CIII/00034

Published
2020

29. Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions

Author

Pol Cuscó, Demian Burguera, Salvatore D'Aniello, Cristina Vicente-García, Bru Cormand, Enrique Navas-Perez, José Luis Ferran, Jordi Garcia-Fernàndez, Carlos Herrera-Úbeda, Marta Alaiz-Noya, Rafael Falcón-Moya, Angel M. Carrión, Serena Mirra, Irene Suárez-Pereira, Gemma Marfany, Fausto Ulloa, Eduardo Soriano, Noèlia Fernàndez-Castillo, Ester Antón-Galindo, Jaime J. Carvajal, Antonio Rodríguez-Moreno, Macarena López-Mayorga, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Junta de Andalucía, Centro de Investigación Biomédica en Red Enfermedades Raras (España), [Navas-Pérez,E, Mirra,S, Burguera,D, Fernàndez-Castillo,N, Antón-Galindo,E, Herrera-Úbeda,C, Cormand,B, Marfany,G, Garcia-Fernàndez,J] Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain. [Vicente-García,C, López-Mayorga,M, Carvajal,JJ] Centro Andaluz de Biología del Desarrollo, CSIC-UPO-JA, Universidad Pablo de Olavide, Sevilla, Spain. [Mirra,S, Ulloa,F, Soriano,E] Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain. [Mirra,S, Marfany,G] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Mirra,S, Soriano,E] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Burguera,D] Department of Zoology, Charles University, Prague, Czech Republic. [Fernàndez-Castillo,N, Marfany,G] Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Barcelona, Spain. [Ferrán,JL] Department of Human Anatomy, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, Murcia, Spain. [Alaiz-Noya,M, Suárez-Pereira,I, Falcón-Moya,R, Rodríguez-Moreno,A, Carrión,AM] Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, Spain. [Alaiz-Noya,M] Present Address: Instituto de Neurociencias de Alicante (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Alicante, Spain. [Suárez-Pereira,I] Present Address: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Neuropsychopharmacology and psychobiology research group, UCA, INiBICA, Cádiz, Spain. [Cuscó,P] Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain. [Cuscó,P] Universitat Pompeu Fabra (UPF), Barcelona, Spain. [D'Aniello,S] Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy. [Soriano,E] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., and Major financial support for this research was received from Spanish 'Ministerio de Ciencia, Innovación y Universidades.' Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish 'Ministerio de Ciencia, Innovación y Universidades'). S.M. was first supported by a contract with the 'Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,' and later by 'Centro de Investigación Biomédica en Red de Enfermedades Raras' (CIBERER). N.F.C. is also under contract by CIBERER. This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.

Subjects
Bex3, Tceal, Placenta, Autism, Genome, Neurodevelopmental disorders, Familia de multigenes, Domestication, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mice, 0302 clinical medicine, Human genetics, Pregnancy, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins [Medical Subject Headings], Gene duplication, Gene cluster, Organisms::Eukaryota::Animals [Medical Subject Headings], Autism spectrum disorder, Genetic novelty, lcsh:QH301-705.5, Serina-treonina quinasas TOR, Phylogeny, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Mice, Knockout, 0303 health sciences, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins [Medical Subject Headings], Genètica humana, Eutheria, TOR Serine-Threonine Kinases, Brain, Nuclear Proteins, DNA-Binding Proteins, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout [Medical Subject Headings], Multigene Family, Placental mammals, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins [Medical Subject Headings], mTOR, Female, Transposon domestication, Transposable element, lcsh:QH426-470, Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders, Pervasive::Autistic Disorder [Medical Subject Headings], Nerve Tissue Proteins, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins [Medical Subject Headings], Biology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors [Medical Subject Headings], Evolution, Molecular, 03 medical and health sciences, Trastornos del neurodesarrollo, Animals, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::TOR Serine-Threonine Kinases [Medical Subject Headings], Allele, Gene, 030304 developmental biology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Research, Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], Anatomy::Embryonic Structures::Placenta [Medical Subject Headings], Phenomena and Processes::Biological Phenomena::Biological Processes::Biological Evolution::Evolution, Molecular [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::CRISPR-Cas Systems [Medical Subject Headings], Mice, Inbred C57BL, lcsh:Genetics, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Interspersed Repetitive Sequences::DNA Transposable Elements [Medical Subject Headings], lcsh:Biology (General), Check Tags::Female [Medical Subject Headings], Evolutionary biology, DNA Transposable Elements, Euterios, Phenomena and Processes::Genetic Phenomena::Phylogeny [Medical Subject Headings], Trastorno del espectro autista, CRISPR-Cas Systems, Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings], Autisme, Apoptosis Regulatory Proteins, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Multigene Family [Medical Subject Headings], 030217 neurology & neurosurgery, Transcription Factors
Abstract

[Background]: One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood., [Results]: Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes., [Conclusions]: We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders., Major financial support for this research was received from Spanish “Ministerio de Ciencia, Innovación y Universidades.” Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish “Ministerio de Ciencia, Innovación y Universidades”). S.M. was first supported by a contract with the “Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,” and later by “Centro de Investigación Biomédica en Red de Enfermedades Raras” (CIBERER). N.F.C. is also under contract by CIBERER.

Published
2020

30. Netrin-1/DCC signaling differentially regulates the migration of Pax7, Nkx6.1, Irx2, Otp and Otx2 cell populations in the developing interpeduncular nucleus

Author

Isabel M. García-Guillén, Antonia Alonso, Nicanor Morales-Delgado, Belén Andrés, Luis Puelles, Guillermina López-Bendito, Faustino Marín, Pilar Aroca, Department of Human Anatomy and Psychobiology, School of Medicine, University of Murcia, Murcia, Spain, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Spain, Department of Histology and Anatomy, School of Medicine, Miguel Hernández University, Alicante, Spain, Instituto de Neurociencias de Alicante, CSIC, Universidad Miguel Hernández, Alicante, Spain., Fundación Séneca, Gobierno de la Región de Murcia, Universidad de Murcia, Agencia Estatal de Investigación (España), and Ministerio de Ciencia, Innovación y Universidades (España)

Subjects
0301 basic medicine, Interpeduncular nucleus, Rhombomere, prodromal, In situ hybridization, Biology, interpeduncular nucleus, 03 medical and health sciences, Cell and Developmental Biology, 0302 clinical medicine, chemoattractant molecules, transcription factors, interpeduncular caudal, isthmus, Netrin, medicine, neuronal tangential migration, rhombomere 2, rhombomere 1, Transcription factor, lcsh:QH301-705.5, DCC, axon guidance, fungi, Netrin1, medial habenula, Cell Biology, Brief Research Report, Cell biology, interpeduncular nucleus (IPN), 030104 developmental biology, medicine.anatomical_structure, rhombomeres, interpeduncular rostral, lcsh:Biology (General), 030220 oncology & carcinogenesis, rhombomere 1 rostral, Axon guidance, IPN, Signal transduction, Nucleus, 5 - Ciencias puras y naturales [CDU], rhombomere 1 caudal, Developmental Biology
Abstract

The interpeduncular nucleus (IPN) is a hindbrain structure formed by three main subdivisions, the prodromal (Pro) domain located at the isthmus (Ist), and the rostral and caudal interpeduncular domains (IPR, IPC) within rhombomere 1 (r1). Various cell populations can be detected in the IPN through the expression of the Nkx6.1, Otp, Otx2, Pax7, and/or Irx2 transcription factors. These cell populations follow independent dorsoventral tangential and radial migratory routes targeting the ventral paramedian region of Ist and r1. Here we set out to examine the influence of the Netrin-1/DCC pathway on these migrations, since it is known to regulate other processes of neuronal migration in the brain. To this end, we analyzed IPN development in late gestational wild-type and DCC–/– mice, using mainly in situ hybridization (ISH) to identify the cells expressing each of the aforementioned genes. We found that the migration of Nkx6.1+ and Irx2+ cells into the Pro domain was strongly disrupted by the loss of DCC, as occurred with the migration of Pax7+, Irx2+, and Otp+ cells that would normally form the IPR. In addition, there was mild impairment of the migration of the Pax7+ and Otx2+ cells that form the IPC. These results demonstrate that the Netrin-1/DCC signaling pathway is involved in the migration of most of the IPN populations, mainly affecting those of the Pro and IPR domains of this nucleus. There are psychiatric disorders that involve the medial habenula (mHb)-IPN system, so that this experimental model could provide a basis to study their neurodevelopmental etiology., This work was funded by the Seneca Foundation to LP (Autonomous Community of Murcia, Excellency Research contract, reference: 19904/GERM/15; 5672 Fundación Séneca; project name: Genoarchitectonic Brain Development and Applications to Neurodegenerative Diseases and Cancer) and by the Knowledge Generation Program of the Spanish Government to GL-B (PGC2018-096631-B-I00). IG-G was recipient of a predoctoral fellowship of the FPU program from the University of Murcia.

Published
2020

31. Methodological approaches to compile and validate a food composition database for methyl-group carriers in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Lode Godderis, Koen Van Herck, Vickà Versele, Sara Pauwels, Pilar Amiano, Joanna L Clasen, Yahya Mahamat-Saleh, Cristina Julián, Corinne Casagrande, Heleen Van Puyvelde, María Dolores Chirlaque, Guri Skeie, Geneviève Nicolas, Marlène De Backer, Inge Huybrechts, Marc J. Gunter, Ghent University Hospital, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Research Foundation - Flanders [Brussel] (FWO), Vrije Universiteit Brussel (VUB), Imperial College Campus of Imperial College Faculty of Medicine, St Mary's Hospital, Praed Street, W2 1NY., Growth, Exercise, NUtrition and Development (GENUD), University of Zaragoza - Universidad de Zaragoza [Zaragoza]-School of Health Sciences, The Arctic University of Norway (UiT), University of Leeds, Molecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB-Arrixaca), University Clinical Hospital 'Virgen de la Arrixaca', University of Murcia, Carretera Buenavista s/n, 30120 El Palmar, Murcia, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Flemish Institute for Technological Research (VITO), Idewe, School of Food Science and Nutrition, University of Leeds, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Movement and Nutrition for Health and Performance, Faculty of Physical Education and Physical Therapy, and Movement and Sport Sciences

Subjects
Folate, Databases, Factual, Population, Choline (PubChem CID: 305), Nutritional Status, EPIC, 247) [Betaine (PubChem CID], 6137) [Methionine (PubChem CID], 01 natural sciences, Analytical Chemistry, Choline, Food composition database, 0404 agricultural biotechnology, 305) [Choline (PubChem CID], Methionine, Betaine (PubChem CID: 247), Neoplasms, Environmental health, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Humans, Prospective Studies, 135398658) [Folate (PubChem CID], education, education.field_of_study, Methyl-group carriers, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 010401 analytical chemistry, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, 3. Good health, 0104 chemical sciences, European Prospective Investigation into Cancer and Nutrition, Methionine (PubChem CID: 6137), Betaine, Nutrition Assessment, Food, Keywords Food composition databaseMethyl-group carriersFolateCholineBetaineMethionineComparative study, Reference database, Folate (PubChem CID: 135398658), Nutrient database, Epic study, Comparative study, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Food Analysis, Food Science, Relative validity
Abstract

Accepted manuscript version, licensed CC BY-NC-ND 4.0. A standardised methodology was used to compile and validate a methyl-group carrier database (MGDB) including folate, choline, betaine and methionine, for use in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Compilation was performed by following structured guidelines to match the EPIC dietary intake data to food items from four food composition databases, according to their assigned priority of use. To assess relative validity, calculated dietary folate intakes were compared between the MGDB and the EPIC nutrient database (ENDB), used as the reference database. Folate intakes based on the MGDB and those generated using the ENDB showed good agreement (weighted κ = 0.63) and were strongly correlated (r = 0.81). This MGDB can be used for investigating potential associations between methyl-group carrier intakes and risk or prognosis of cancer and other diseases in the EPIC study population.

Published
2020

32. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort

Author

Agnès Fournier, Eva Lundin, N. Charlotte Onland-Moret, Louise Hansen, Elisavet Valanou, Marina Kvaskoff, Leire Gil, Inger T. Gram, Rosario Tumino, Marc J. Gunter, Annika Idahl, Rudolf Kaaks, Noemi Bender, Eric J. Duell, María José Sánchez, Carlotta Sacerdote, Kristian Riesbeck, Sandra González Maldonado, Claudia Agnoli, Anne Tjønneland, Charlotte Le Cornet, Renée T. Fortner, Laure Dossus, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Antonia Trichopoulou, Amalia Mattiello, José Ramón Quirós, Aurelio Barricarte, Maria Dolores Chirlaque, Tim Waterboer, Eleni Peppa, Domenico Palli, Jenny Brändstedt, Kay-Tee Khaw, Aurora Perez-Cornago, Heiner Boeing, Umeå University, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Danish Cancer Society Research Center, Copenhagen, Denmark, parent, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Hellenic Health Foundation, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, I-20133 Milano, Italy, University of Naples Federico II, Civile - M.P.Arezzo Hospital, Center for Cancer Prevention (CPO-Piemonte), Universiteit Utrecht, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France. Electronic address: steliarova@iarc.fr., Catalan Institute of Oncology (ICO-IDIBELL), Hospitales Universitarios de Granada/Universidad de Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Public Health Institute of Navarra, Pamplona, Spain, and CIBER Epidemiología y Salud Pública (CIBERESP), IdiSNA, Navarra Institute for Health Research, Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Skane University Hospital [Lund], Department of Translational Medicine [Malmö, Sweden] (Clinical Microbiology), Lund University [Lund, Sweden], University of Cambridge [UK] (CAM), University of Oxford [Oxford], Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, C570/A16491 VetenskapsrÃ¥det, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS CAN 2016/545 German Cancer Research Center, DKFZ National Research Council, NRC Cancer Research Foundation in Northern Sweden European Commission, EC Centre International de Recherche sur le Cancer, IARC RD06/0020 German Cancer Research Center, DKFZ Cancerfonden PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC-2009-AdG 232997 NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Medical Research Council, MRC: MR/M012190/1, This work was supported by grants from The Cancer Research Foundation in Northern Sweden and The County Council of V?sterbotten, Sweden, and the German Cancer Research Center. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Additional funding received from the Anna and Edwin Berger Foundation (K.R.), Malm? Hospital Cancer Foundation (K.R.), Cancerfonden (CAN 2016/545 to K.R.).

Subjects
Oncology, Cancer Research, endocrine system diseases, Càncer d'ovari, Chlamydia trachomatis, Mycoplasma genitalium, Carcinoma, Ovarian Epithelial, medicine.disease_cause, Serology, 0302 clinical medicine, Risk Factors, Pelvic inflammatory disease, Prospective Studies, human papillomavirus, Aged, 80 and over, Ovarian Neoplasms, Sexually transmitted diseases, Human papillomavirus 16, Chlamydia, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, biology, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, ovarian cancer, 030220 oncology & carcinogenesis, Female, Malalties de transmissió sexual, Adult, Risk, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Ovarian cancer, Internal medicine, medicine, Humans, Neoplastic transformation, Aged, business.industry, Papillomavirus Infections, Chlamydia Infections, biology.organism_classification, medicine.disease, herpes simplex virus, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Relative risk, Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Biomarkers
Abstract

International audience; A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.

Published
2020

33. Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author

Christina C. Dahm, Marc J. Gunter, Carlotta Sacerdote, Carmen Santiuste, Sabine Rohrmann, Merete Ellingjord-Dale, Cecilie Kyrø, Anika Hüsing, Renée T. Fortner, Eva Ardanaz, Antonia Trichopoulou, María Dolores López, Claudia Agnoli, Elisabete Weiderpass, Virginia Menéndez, Rudolf Kaaks, Signe Borgquist, Marina Kvaskoff, Patrick Arveux, Anne Tjønneland, Carlo La Vecchia, Helene Tilma Vistisen, Marije F. Bakker, Antonio Agudo, María José Sánchez, Agnès Fournier, Laure Dossus, Kay-Tee Khaw, Timothy J. Key, Guri Skeie, Eleni Peppa, Rosario Tumino, Elio Riboli, Salma Butt, Carla H. van Gils, Nena Karavasiloglou, Kostantinos K. Tsilidis, Tilman Kühn, Giovanna Masala, Inge Huybrechts, Matthias B. Schulze, Domenico Palli, Anna Karakatsani, Jenny Chang-Claude, Salvatore Panico, Apollo - University of Cambridge Repository, [Karavasiloglou,N, Rohrmann,S] Division of Chronic Disease Epidemiology, Institute for Epidemiology, Biostatistics and Prevention, University of Zurich, Zurich, Switzerland. [Karavasiloglou,N, Rohrmann,S] Cancer Registry Zurich and Zug, University Hospital Zurich, Zurich, Switzerland. [Karavasiloglou,N, Hüsing,A, Turzanski Fortner,R, Chang-Claude,J, Kaaks,R, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Masala,G, Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [van Gils,CH, Bakker,MF] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Huybrechts,I, Weiderpass,E, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Weiderpas,E, Skeie,G] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Arveux,P, Fournier,A, Kvaskoff,M] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Arveux,P, Kvaskoff,M] Gustave Roussy, Villejuif, France. [Arveux,P] Breast and Gynaecologic Cancer Registry of Côte d’Or, Georges-François Leclerc Cancer Centre, UNICANCER, Dijon, France. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Tjønneland,A, Kyrø,C] Danish Cancer Society Research Center, Copenhagen, Denmark. [Dahm,CC, Vistisen,HT] Department of Public Health, Aarhus University, Aarhus, Denmark. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [Sánchez,MJ, Chirlaque López,MD, Santiuste,C, Ardanaz,E] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Chirlaque López,MD, Santiuste,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque López,MD] Department of Health and Social Sciences, Murcia University, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Trichopoulou,A, Karakatsani,A, La Vecchia,C, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [La Vecchia,C] Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Panico,S] Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Azienda Sanitaria Provinciale (ASP), Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Butt,ST] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Butt,ST] Department of Surgery, Skåne University Hospital, Malmö, Sweden. [Borgquist,S] Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark. [Borgquist,S] Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Schulze,M] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is supported financially by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center (German Cancer Research Center), Federal Ministry of Education and Research (Federal Ministry of Education and Research), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (Ministry of Health, Welfare and Sport), Netherlands Cancer Registry (Netherlands Cancer Registry), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO, Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Tjønneland, Anne [0000-0003-4385-2097], Dahm, Christina C [0000-0003-0481-2893], Tumino, Rosario [0000-0003-2666-414X], and Borgquist, Signe [0000-0001-7938-8893]

Subjects
0301 basic medicine, Male, Breastfeeding, lcsh:Medicine, Breast carcinoma in situ, GUIDELINES, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Medicine(all), Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings], Hazard ratio, Academies and Institutes, Cohort, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Lifestyle Score, Europe, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Female, CONCORDANCE, Life Sciences & Biomedicine, PROJECT, In situ breast cancer, Cohort study, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Estudios de cohortes, RECREATIONAL PHYSICAL-ACTIVITY, Check Tags::Male [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Data Collection::Nutrition Assessment [Medical Subject Headings], Breast Neoplasms, Estilo de vida, Càncer de mama, 03 medical and health sciences, Medicine, General & Internal, Medicina preventiva, DIETARY, General & Internal Medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Carcinoma de mama in situ, Preventive medicine, 030109 nutrition & dietetics, Cancer prevention, Science & Technology, business.industry, Prevention, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Lifestyle, United States, VDP::Medical disciplines: 700, Nutrition Assessment, Health Care::Health Care Economics and Organizations::Organizations::Academies and Institutes [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer research, Life style, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], business
Abstract

Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

Published
2019

34. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author

José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract

BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Published
2019

35. Lectin binding pattern of glycoconjugates during spontaneous testicular recrudescence in Syrian hamster (Mesocricetus auratus) after exposure to short photoperiod

Author

Jesús Martínez-Hernández, Ester Beltrán-Frutos, C Ferrer, Luis Miguel Pastor, María Isabel Serrano-Sánchez, V Seco-Rovira, and Department of Cell Biology and Histology, Medical School, IMIB-Arrixaca, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Spain

Subjects
0301 basic medicine, Male, 6 - Ciencias aplicadas [CDU], endocrine system, Glycoconjugate, Urology, Photoperiod, Hamster, Apoptosis, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Recurrence, Cricetinae, Lectins, Testis, medicine, Animals, Acrosome, chemistry.chemical_classification, 030219 obstetrics & reproductive medicine, biology, Mesocricetus, urogenital system, Chemistry, Glycoconjugates. Lectins. Hamster. Apoptosis. Recrudescence, Lectin, General Medicine, Sertoli cell, biology.organism_classification, Molecular biology, Spermatids, Epithelium, 030104 developmental biology, medicine.anatomical_structure, Seminiferous Epithelium, biology.protein, Glycoconjugates, Germ cell
Abstract

© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Andrologia]. To access the final edited and published work see [10.1111/and.13148] Lectin histochemistry was used to characterize glycoconjugates and cellular apoptosis in the seminiferous epithelium and interstitium of hamster testis during spontaneous recrudescence. An increase in the LTA lectin affinity was observed in spermatids in the Golgi phase. An increase in labelling of PNA and Con-A lectin in acrosome of spermatids (acrosome phase) as well increased labelling with Con-A in spermatids (cap phase) was observed. Spermatocytes showed decreased affinity with PNA and AAA lectins and an increase in positivity for LTA and GNA lectins. Spermatogonia showed a slight decrease in positivity to WGA and an increase in labelling with Con-A, and a decreased affinity for the AAA lectin. At the end of recrudescence all these germinal cells showed a similar pattern to the control. The Sertoli cells showed a gradual decrease in labelling with the GNA lectin and the Leydig cells an increase in labelling with Con-A and GNA. Particularly unusual was the observation of apoptotic spermatocytes and spermatids positive for PNA, GNA, AAA and Con-A, together with spermatocytes positive to LTA. In conclusion the normal lectin pattern is recovered during testis recrudescence and germ cell apoptotic activity is low, as is observed by specific lectins for germ cells in apoptosis.

Published
2019

36. Development and validation of circulating CA125 prediction models in postmenopausal women

Author

J. Ramón Quirós, N. Charlotte Onland-Moret, Anna Karakatsani, Marina Kvaskoff, Raina N. Fichorova, Pilar Amiano, Eva Lundin, Louise Hansen, Kathryn L. Terry, Sara Grioni, Kay-Tee Khaw, Leila Lujan-Barroso, Amalia Mattiello, Renée T. Fortner, Agnès Fournier, Linda J. Titus, Rudolf Kaaks, Sandra Colorado-Yohar, Anne Tjønneland, Timothy J. Key, Marc J. Gunter, Aurelio Barricarte, Shelley S. Tworoger, Laure Dossus, Britton Trabert, Naoko Sasamoto, Inger T. Gram, David C. Muller, Hanna Sartor, Bernard Rosner, Allison F. Vitonis, Francesca Mancini, Eleni Peppa, Valentina Fiano, María José Sánchez, Heiner Boeing, Daniel W. Cramer, Ana Babic, Hidemi S. Yamamoto, Rosario Tumino, Nicolas Wentzensen, Domenico Palli, Annika Idahl, Elisabete Weiderpass, Antonia Trichopoulou, Elio Riboli, Sasamoto, Naoko [0000-0002-4526-2181], Tjønneland, Anne [0000-0003-4385-2097], Tumino, Rosario [0000-0003-2666-414X], Apollo - University of Cambridge Repository, [Sasamoto,N, Vitonis,AF, Cramer,DW, Terry,KL] Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, USA. [Babic,A] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Rosner,BA] Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Fortner,RT, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Yamamoto,H, Fichorova,RN] Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, USA.[Titus,LJ] Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Hanover, NH, USA. [Tjønneland,A, Hansen,L] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Kvaskoff,M, Fournier,A, Mancini,FR] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Kvaskoff,M, Mancini,FR] Gustave Roussy, Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Peppa,E, Karakatsani,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'Civic - M.P. Arezzo'Hospital, ASP, Ragusa, Italy. [Fiano,V] Unit of Cancer Epidemiology– CeRMS, Department of Medical Sciences, University of Turin, Turin, Italy. [Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. [Weiderpass,E, Gunter,M, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Gram,IT] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Lujan-Barroso,L] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L’ Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA). Universidad de Granada, Granada, Spain. [Sánchez,MJ, Colorado-Yohar,S, Barricarte,A, Amiano,P] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Colorado-Yohar,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Colorado-Yohar,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Barricarte,A] Navarra Public Health Institute, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Lundin,E] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Sartor,H] Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden. [Sartor,H] Department of Translational Medicine, Lund University, Lund, Sweden. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Muller,D, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Trabert,B, Wentzensen,N] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, D.C, USA. [Tworoger,SS] Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA. [Tworoger,SS, Terry,KL] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Research reported in this publication was supported by U.S. National Institutes of Health under the following award numbers: R01 CA193965 (to K.L. Terry), R01 CA 158119 and R35 CA197605 (to D.W. Cramer), P01 CA087969 (to S.S. Tworoger), UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, and supported in part by the intramural research program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
Antígeno Ca-125, Oncology, endocrine system diseases, medicine.medical_treatment, Càncer d'ovari, Ovarian neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings], 0302 clinical medicine, Neoplasms, PROSTATE, 030212 general & internal medicine, CA-125, Early Detection of Cancer, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, RISK, Reproductive Biology, Biochemical markers, Obstetrics and Gynecology, Early detection, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Early diagnosis, female genital diseases and pregnancy complications, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menopause, Postmenopause, Posmenopausia, 030220 oncology & carcinogenesis, Marcadors bioquímics, Biomarker (medicine), Female, Postmenopausal, Life Sciences & Biomedicine, Menopausa, medicine.medical_specialty, Neoplasias ováricas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Early Diagnosis::Early Detection of Cancer [Medical Subject Headings], BIOMARKERS, CA125, Ovarian cancer, Prediction model, Reproduktionsmedicin och gynekologi, lcsh:Gynecology and obstetrics, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm::Antigens, Tumor-Associated, Carbohydrate::CA-125 Antigen [Medical Subject Headings], OVARIAN-CANCER, 03 medical and health sciences, Diagnóstico precoz, Internal medicine, Obstetrics, Gynecology and Reproductive Medicine, medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Sexual Development::Climacteric::Menopause::Postmenopause [Medical Subject Headings], lcsh:RG1-991, Aged, Hysterectomy, Science & Technology, business.industry, Research, Case-control study, CANCER SCREENING TRIAL, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Stepwise regression, Models, Theoretical, medicine.disease, VDP::Medical disciplines: 700, Detección precoz del cáncer, Check Tags::Female [Medical Subject Headings], CA-125 Antigen, Hormone therapy, business, Body mass index, LUNG
Abstract

Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

Published
2019

37. Editorial overview: Ion channels and immune cells: What ions could do for immune cells

Author

Florence Velge-Roussel, Pablo Pelegrín, Laboratoire d'immunologie parasitaire, Université Francois Rabelais [Tours]-UFR de Sciences Pharmaceutiques [Tours], Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), and Molecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB-Arrixaca), University Clinical Hospital 'Virgen de la Arrixaca', University of Murcia, Carretera Buenavista s/n, 30120 El Palmar, Murcia, Spain

Subjects
Ions, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Immunology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Ion Channels, Ion, Cell biology, Immune system, Immune System, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Animals, Humans, Ion channel, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

38. Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster during spontaneous recrudescence after exposure to short photoperiod

Author

María Del Mar Sánchez-Huertas, V Seco-Rovira, Luis Miguel Pastor, Ester Beltrán-Frutos, Jesús Martínez-Hernández, C Ferrer, Manuel Canteras, and 1Department of Cell Biology and Histology, Medical School, IMIB-Arrixaca, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Spain. 2Department of Statistics, Medical School, University of Murcia, Murcia, Spain.

Subjects
Male, 0301 basic medicine, 6 - Ciencias aplicadas [CDU], endocrine system, Spermiogenesis, Photoperiod, Hamster, Apoptosis, Andrology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Microscopy, Electron, Transmission, Recurrence, Proliferating Cell Nuclear Antigen, In Situ Nick-End Labeling, medicine, Animals, Spermatogenesis, Testes, Photoperiod, Apoptosis, Proliferation, Recrudescence, Andrology, 030219 obstetrics & reproductive medicine, Mesocricetus, biology, Chemistry, biology.organism_classification, Spermatozoa, Epithelium, Proliferating cell nuclear antigen, Seminiferous Epithelium, 030104 developmental biology, medicine.anatomical_structure, Terminal deoxynucleotidyl transferase, biology.protein, Animal Science and Zoology, Biotechnology
Abstract

© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in [Reproduction in domestic animals]. To access the final edited and published work see [10.1111/rda.13201].” Syrian hamsters are photoperiodic rodents in which reproduction, including testicular function, is stimulated by long photoperiod exposure and curtailed by exposure to a short photoperiod. The objectives of this study were to characterize the testis histomorphometrically and to determine the role of the proliferation and apoptosis phenomena in the recovery of the seminiferous epithelium during spontaneous recrudescence after exposure to short photoperiod. The study was performed using conventional light microscopy, proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling staining, image analysis software, and transmission electron microscopy in three recrudescence groups: initial recrudescence (IR), advanced recrudescence (AR), and total recrudescence (TR). Morphometrically, the results pointed to the gradual recovery of the testicular and tubular volumes, as well as of the seminiferous epithelium. Among the IR and AR groups, the increase in testicular and tubular volumes was accompanied by an increase in tubular diameter and length, with an increase in interstitial volume. From AR to TR, there was an increase in the tubular and total volumes, but, in this case, with a gradual increase in tubular diameter. Recovery of the seminiferous epithelium was accompanied by changes in apoptosis and proliferation activities. The first decreased half way through the process and the second remained higher than the control levels throughout the recrudescence stage. Ultrastructurally, alterations in the spermatozoa were observed, which indicated that spermiogenesis was not yet completely normal. In conclusion, spontaneous testicular recrudescence in Syrian hamster comprises two histomorphometrical phases, the first related to an increase in tubular length and diameter and interstitial volume, and the second depending principally on the gradual increase in tubular diameter. The restoration of the seminiferous epithelium is due to apoptosis reaching normal values in the AR group accompanied by higher proliferative activity than that observed in the Control group.

Published
2018

39. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author

Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J., Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Metabolism Section, International Agency for Research on Cancer, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Registry of Norway, Institute of Population-Based Cancer Research, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Public Health, Section for Epidemiology, Aarhus University [Aarhus], Danish Cancer Society Research Center, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition (DIfE), 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], Hellenic Health Foundation, Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Cancer registry and histopathology unit, Civile - M.P.Arezzo Hospital, Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital-Center for Cancer Prevention (CPO-Piemonte), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], School of Public Health - Department of Epidemiology and Biostatistics, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Julius Center for Health Sciences and Primary Care, Department of Nutrition [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Public Health Directorate Asturias, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Facultat de Ciències de la Salut Blanquerna, Universitat Ramon Llull [Barcelona] (URL), Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Public Health Institute of Navarra, IdiSNA, Navarra Institute for Health Research, Public Health Department of Gipuzkoa, Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Nutritional Epidemiology, Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy, University of Gothenburg (GU), Department of Odontology, Umeå University, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, Institute of Metabolic Science, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, French National Cancer Institute (INCa)-Canceropole Ile-de-France [2017-1-PL SHS-01-INSERM ADR 5-1], European Commission (DG-SANCO), Danish Cancer Society (Denmark), Ligue Contre le Cancer, (France), Institut Gustave Roussy, (France), Mutuelle Generale de l'Education Nationale, (France), Institut National de la Sante et de la Recherche Medicale (Inserm), (France), Deutsche Krebshilfe (Germany), Deutsches Krebsforschungszentrum (Germany), Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Dutch Ministry of Public Health, Welfare, and Sports (VWS) (the Netherlands), Netherlands Cancer Registry (NKR) (the Netherlands), LK Research Funds (the Netherlands), Dutch Prevention Funds (the Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands), World Cancer Research Fund (WCRF) (the Netherlands), Statistics Netherlands (the Netherlands), Health Research Fund (FIS) [PI13/00061], Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) [6236], Regional Government of Navarra, ISCIII RETIC (Spain) [RD06/0020], Swedish Cancer Society (Sweden), Swedish Scientific Council (Sweden), County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK [14136, C570/A16491, C8221/A19170], Medical Research Council [1000143, MR/M012190/1], National Research Council (Italy), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), 'CIVIC-M.P. AREZZO' Hospital, University of Oxford, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Deschasaux, Mélanie [0000-0002-3359-420X], Huybrechts, Inge [0000-0003-3838-855X], Murphy, Neil [0000-0003-3347-8249], Hercberg, Serge [0000-0002-3168-1350], Srour, Bernard [0000-0002-1277-3380], Kesse-Guyot, Emmanuelle [0000-0002-9715-3534], Weiderpass, Elisabete [0000-0003-2237-0128], Dahm, Christina C [0000-0003-0481-2893], Kyrø, Cecilie [0000-0002-9083-8960], Olsen, Anja [0000-0003-4788-503X], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Mahamat-Saleh, Yahya [0000-0002-5892-8886], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Hjartåker, Anette [0000-0003-3002-4030], Skeie, Guri [0000-0003-2476-4251], Jakszyn, Paula [0000-0003-0672-8847], Huerta, José María [0000-0002-9637-3869], Sonestedt, Emily [0000-0002-0747-4562], Johansson, Ingegerd [0000-0002-9227-8434], Wareham, Nick [0000-0003-1422-2993], Bradbury, Kathryn E [0000-0003-3345-7333], Perez-Cornago, Aurora [0000-0002-5652-356X], Riboli, Elio [0000-0001-6795-6080], Touvier, Mathilde [0000-0002-8322-8857], Apollo - University of Cambridge Repository, Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C, Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Luka, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Ba, Peeters, Petra H, Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J, Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Perez-Cornago, Aurora, Tsilidis, Konstantinos K, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, and Touvier, Mathilde

Subjects
Adult, Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nutrition Policy, Cohort Studies, Food Preferences, Medicine, General & Internal, project, Food Labeling, Risk Factors, front-of-package, su.vi.max cohort, General & Internal Medicine, Neoplasms, Humans, french adults, Prospective Studies, dietary index, database, Medicine(all), validation, Nutrition and Dietetics, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 11 Medical And Health Sciences, Middle Aged, Näringslära, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Europe, prospective association, 3121 General medicine, internal medicine and other clinical medicine, Medicine, Female, cardiovascular-disease risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Life Sciences & Biomedicine, Nutritive Value, france, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Source at https://doi.org/10.1371/journal.pmed.1002651. Background - Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings - This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992–2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03–1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions - In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

Published
2018

40. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author

Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Subjects
0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Published
2017

41. Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain

Author

Nerea Fernández de Larrea-Baz, Angelika Michel, Beatriz Romero, Beatriz Pérez-Gómez, Victor Moreno, Vicente Martín, Trinidad Dierssen-Sotos, José J. Jiménez-Moleón, Jesús Castilla, Adonina Tardón, Irune Ruiz, Rosana Peiró, Antonio Tejada, María D. Chirlaque, Julia A. Butt, Rocío Olmedo-Requena, Inés Gómez-Acebo, Pedro Linares, Elena Boldo, Antoni Castells, Michael Pawlita, Gemma Castaño-Vinyals, Manolis Kogevinas, Silvia de Sanjosé, Marina Pollán, Rosa del Campo, Tim Waterboer, Nuria Aragonés, [Fernandez de Larrea-Baz, Nerea] Inst Salud Carlos III, Area Natl Ctr Epidemiol, Environm & Canc Epidemiol Area, Madrid, Spain, [Perez-Gomez, Beatriz] Inst Salud Carlos III, Area Natl Ctr Epidemiol, Environm & Canc Epidemiol Area, Madrid, Spain, [Aragones, Nuria] Inst Salud Carlos III, Area Natl Ctr Epidemiol, Environm & Canc Epidemiol Area, Madrid, Spain, [Fernandez de Larrea-Baz, Nerea] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Dierssen-Sotos, Trinidad] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Jimenez-Moleon, Jose J.] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Castilla, Jesus] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Tardon, Adonina] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Peiro, Rosana] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Chirlaque, Maria D.] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Olmedo-Requena, Rocio] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Gomez-Acebo, Ines] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Boldo, Elena] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Castano-Vinyals, Gemma] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Kogevinas, Manolis] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [de Sanjose, Silvia] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Pollan, Marina] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Aragones, Nuria] CIBERESP, CIBER Epidemiol & Publ Hlth, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid, Spain, [Michel, Angelika] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect Infect Inflammat, Heidelberg, Germany, [Butt, Julia A.] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect Infect Inflammat, Heidelberg, Germany, [Pawlita, Michael] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect Infect Inflammat, Heidelberg, Germany, [Waterboer, Tim] German Canc Res Ctr, Div Mol Diagnost Oncogen Infect Infect Inflammat, Heidelberg, Germany, [Perez-Gomez, Beatriz] Ramon & Cajal Univ Hosp IRYCIS, Dept Microbiol, Madrid, Spain, [del Campo, Rosa] Ramon & Cajal Univ Hosp IRYCIS, Dept Microbiol, Madrid, Spain, [Perez-Gomez, Beatriz] IIS Puerta Hierro, Puerta Hierro Hlth Res Inst, Canc Epidemiol Res Grp Oncol & Hematol Area, Madrid, Spain, [Boldo, Elena] IIS Puerta Hierro, Puerta Hierro Hlth Res Inst, Canc Epidemiol Res Grp Oncol & Hematol Area, Madrid, Spain, [Pollan, Marina] IIS Puerta Hierro, Puerta Hierro Hlth Res Inst, Canc Epidemiol Res Grp Oncol & Hematol Area, Madrid, Spain, [Moreno, Victor] Hosp Llobregat, Catalan Inst Oncol, Canc Prevent & Control Program, Barcelona, Spain, [Moreno, Victor] Univ Barcelona, Fac Med, Dept Clin Sci, Barcelona, Spain, [Moreno, Victor] Hosp Llobregat, Bellvitge Biomed Res Inst IDIBELL, Colorectal Canc Grp, Barcelona, Spain, [Martin, Vicente] Univ Leon, Res Grp Gene Environm & Hlth Interact, Leon, Spain, [Martin, Vicente] Univ Leon, Fac Hlth Sci, Dept Biomed Sci, Area Prevent Med & Publ Hlth, Leon, Spain, [Dierssen-Sotos, Trinidad] Univ Cantabria IDIVAL, Sch Med, Div Epidemiol & Computat Biol, Santander, Spain, [Jimenez-Moleon, Jose J.] Inst Invest Biosanitaria Granada, Granada Hlth Res Inst ibs GRANADA, Granada, Spain, [Olmedo-Requena, Rocio] Inst Invest Biosanitaria Granada, Granada Hlth Res Inst ibs GRANADA, Granada, Spain, [Jimenez-Moleon, Jose J.] Univ Granada, Dept Prevent Med & Publ Hlth, Granada, Spain, [Olmedo-Requena, Rocio] Univ Granada, Dept Prevent Med & Publ Hlth, Granada, Spain, [Castilla, Jesus] Inst Salud Publ Navarra, IdiSNA Navarra Inst Hlth Res, Pamplona, Spain, [Tardon, Adonina] Univ Oviedo, Oncol Inst, Dept Med, Mol Epidemiol Canc Unit, Oviedo, Spain, [Ruiz, Irune] Donostia Univ Hosp, Dept Pathol, Donostia San Sebastian, Spain, [Peiro, Rosana] Fdn Promot Hlth & Biomed Res Valencia Reg FISABIO, Fdn La Fomento Invest Sanitaria & Biomed Comunita, Valencia, Spain, [Tejada, Antonio] Huelva Univ, Hosp Complex, Dept Gen Surg, Coloproctol Unit, Huelva, Spain, [Chirlaque, Maria D.] IMIB Arrixaca, Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Chirlaque, Maria D.] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain, [Linares, Pedro] Univ Leon, Dept Gastroenterol & Hepatol Complejo Asis, Leon, Spain, [Castells, Antoni] Hosp Clin Barcelona, Gastroenterol Dept, Barcelona, Spain, [Castells, Antoni] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain, [Castells, Antoni] CIBER Enfermed Hepat & Digestivas CIBEREHD, CIBER Liver & Digest Dis, Madrid, Spain, [Castells, Antoni] Univ Barcelona, Dept Gastroenterol, Barcelona, Spain, [Castano-Vinyals, Gemma] ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain, [Kogevinas, Manolis] ISGlobal, Ctr Res Environm Epidemiol CREAL, Barcelona, Spain, [Castano-Vinyals, Gemma] Hosp Mar, Med Res Inst IMIM, Barcelona, Spain, [Kogevinas, Manolis] Hosp Mar, Med Res Inst IMIM, Barcelona, Spain, [Castano-Vinyals, Gemma] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain, [Kogevinas, Manolis] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain, [de Sanjose, Silvia] Hosp Llobregat, Catalan Inst Oncol IDIBELL, Canc Epidemiol & Res Program, Barcelona, Spain, [del Campo, Rosa] Red Espanola Invest Patol Infecciosa, Spanish Network Res Infect Dis, Seville, Spain, 'Accion Transversal del Cancer', Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III grants, FEDER funds-a way to build Europe, Fundacion Marques de Valdecilla, Catalan Government DURSI, Junta de Castilla y Leon, Consejeria de Salud of the Junta de Andalucia, Regional Government of the Basque Country, Conselleria de Sanitat of the Generalitat Valenciana, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, Instituto de Salud Carlos III, Fundación Marqués de Valdecilla, Government of Catalonia (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Basque Government (España), and Universitat de Barcelona

Subjects
Microbiology (medical), medicine.medical_specialty, Medicina, Population, Helicobacteri pilòric, lcsh:QR1-502, Colon neoplasia, Gastroenterology, Microbiology, lcsh:Microbiology, Serology, Association, Colorectal neoplasm, 03 medical and health sciences, 0302 clinical medicine, Càncer colorectal, Bacterial infections, Internal medicine, Epidemiology, Non-infectious diseases, medicine, CagA, Risk factor, education, Multiplex serology, Original Research, education.field_of_study, biology, Helicobacter pylori, business.industry, Carcinoma, Case-control study, Odds ratio, Metaanalysis, biology.organism_classification, Colorectal cancer, Gastric-cancer, Chronic infection, 030220 oncology & carcinogenesis, Immunology, 030211 gastroenterology & hepatology, business, Infection
Abstract

Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain. Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to >= 4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71-1.16). Among H. pylori seropositive subjects, seropositivity to Cag delta showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified., The study was supported by the "Accion Transversal del Cancer," approved on the Spanish Ministry Council on the 11th October 2007, by the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), by the Instituto de Salud Carlos III grants, co-funded by FEDER funds-a way to build Europe-(grants PI08/1770, PI09/0773, PI09/1286, PI09/1903, PI09/2078, PI09/1662, PI11/01403, PI14/00613, PI14/01219, and PI15/00069), by the Fundacion Marques de Valdecilla (grant API 10/09), by Catalan Government DURSI (grants 2014SGR647 and 2014SGR756), by the Junta de Castilla y Leon (grant LE22A10-2), by the Consejeria de Salud of the Junta de Andalucia (grant 2009-S0143), by the Regional Government of the Basque Country, and by the Conselleria de Sanitat of the Generalitat Valenciana (grant AP061/10). The funders had no role in the study design, data analysis, data interpretation or writing the manuscript.

Published
2017

42. Inflammasome Regulates Hematopoiesis through Cleavage of the Master Erythroid Transcription Factor GATA1

Author

Sylwia D. Tyrkalska, Irene Pardo-Sánchez, Francisco J. Martínez-Navarro, Nouraiz Ahmed, Ana B. Pérez-Oliva, Francisco J. Martínez-Morcillo, Avik Choudhuri, Victoriano Mulero, Francisca Alcaraz-Pérez, Christophe Lachaud, Leonard I. Zon, Lola Rodríguez-Ruiz, Marlies P. Rossmann, Azucena López-Muñoz, Timm Schroeder, María L. Cayuela, Sergio Candel, Diana García-Moreno, IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Biosystems Science and Engineering [ETH Zürich] (D-BSSE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Harvard University, Division of Hematology-Oncology [Boston, MA, USA] (Boston Children’s Hospital), Harvard Medical School [Boston] (HMS), Dana-Farber Cancer Institute [Boston], This work was supported by the Spanish Ministry of Science, Innovation and Universities (grants BIO2014-52655-R and BIO2017-84702-R to VM and PI13/0234 to MLC, PhD fellowship to FJMM and Juan de 383 la Cierva postdoctoral contract to FAP), all co-funded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds), Fundación Séneca-Murcia (grant 19400/PI/14 to MLC), the University of Murcia (postdoctoral contracts to ABPO and DGM, and PhD fellowship to FJMM), SNF grant 179490 to TS, and the European 7th Framework Initial Training Network FishForPharma (PhD fellowship to SDT, PITG-GA-2011-289209)., European Project: 289209,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,FISHFORPHARMA(2012), Hospital Clínico Universitario Virgen de la Arrixaca [Murcia, Spain], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Harvard University [Cambridge], lachaud, christophe, and Training Network on Zebrafish Infection Models for Pharmaceutical Screens - FISHFORPHARMA - - EC:FP7:PEOPLE2012-01-01 - 2015-12-31 - 289209 - VALID

Subjects
Male, 0301 basic medicine, Myeloid, Neutrophils, Inflammasomes, [SDV]Life Sciences [q-bio], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Animals, Genetically Modified, Fish Diseases, Mice, 0302 clinical medicine, hemic and lymphatic diseases, Immunology and Allergy, GATA1 Transcription Factor, Zebrafish, biology, Caspase 1, Gene Expression Regulation, Developmental, Cell Differentiation, GATA1, Inflammasome, anemia, Cell biology, [SDV] Life Sciences [q-bio], Haematopoiesis, Infectious Diseases, medicine.anatomical_structure, Caspase-1, 030220 oncology & carcinogenesis, Erythropoiesis, Myelopoiesis, medicine.drug, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, 03 medical and health sciences, Erythroid Cells, inflammasome, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, mouse, Inflammation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Zebrafish Proteins, zebrafish, biology.organism_classification, Immunity, Innate, neutrophilic inflammation, Hematopoiesis, Mice, Inbred C57BL, 030104 developmental biology, Proteolysis, K562 Cells
Abstract

International audience; Chronic inflammatory diseases are associated with altered hematopoiesis that could result in neutrophilia and anemia. Here we report that genetic or chemical manipulation of different inflammasome components altered the differentiation of hematopoietic stem and progenitor cells (HSPC) in zebrafish. Although the inflammasome was dispensable for the emergence of HSPC, it was intrinsically required for their myeloid differentiation. In addition, Gata1 transcript and protein amounts increased in inflammasome-deficient larvae, enforcing erythropoiesis and inhibiting myelopoiesis. This mechanism is evolutionarily conserved, since pharmacological inhibition of the inflammasome altered erythroid differentiation of human erythroleukemic K562 cells. In addition, caspase-1 inhibition rapidly upregulated GATA1 protein in mouse HSPC promoting their erythroid differentiation. Importantly, pharmacological inhibition of the inflammasome rescued zebrafish disease models of neutrophilic inflammation and anemia. These results indicate that the inflammasome plays a major role in the pathogenesis of neutrophilia and anemia of chronic diseases and reveal druggable targets for therapeutic interventions.

Published
2019

43. Meal patterns across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study

Author

E Huseinovic, A Winkvist, N Slimani, MK Park, H Freisling, H Boeing, G Buckland, L Schwingshackl, E Weiderpass, AL Rostgaard-Hansen, A Tjønneland, A Affret, MC Boutron-Ruault, G Fagherazzi, V Katzke, T Kühn, A Naska, P Orfanos, A Trichopoulou, V Pala, D Palli, F Ricceri, M Santucci de Magistris, R Tumino, D Engeset, T Enget, G Skeie, A Barricarte, CB Bonet, MD Chirlaque, P Amiano, JR Quirós, MJ Sánchez, JA Dias, I Drake, M Wennberg, JMA Boer, MC Ocké, WMM Verschuren, C Lassale, A Perez-Cornago, E Riboli, H Ward, H Bertéus Forslund, [Huseinovic, E.] Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Box 459, SE-40530 Gothenburg, Sweden, [Winkvist, A.] Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Box 459, SE-40530 Gothenburg, Sweden, [Forslund, H. Berteus] Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Box 459, SE-40530 Gothenburg, Sweden, [Winkvist, A.] Umea Univ, Nutr Res, Dept Publ Hlth & Clin Med, Umea, Sweden, [Wennberg, M.] Umea Univ, Nutr Res, Dept Publ Hlth & Clin Med, Umea, Sweden, [Slimani, N.] Int Agcy Res Canc, Dietary Exposure Assessment Grp, Lyon, France, [Park, M. K.] Int Agcy Res Canc, Dietary Exposure Assessment Grp, Lyon, France, [Freisling, H.] Int Agcy Res Canc, Dietary Exposure Assessment Grp, Lyon, France, [Boeing, H.] German Inst Human Nutr, Dept Epidemiol, Nuthetal, Germany, [Schwingshackl, L.] German Inst Human Nutr, Dept Epidemiol, Nuthetal, Germany, [Buckland, G.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr & Canc, Canc Epidemiol Res Programme, Barcelona, Spain, [Bonet, C. B.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr & Canc, Canc Epidemiol Res Programme, Barcelona, Spain, [Weiderpass, E.] Univ Tromso, Arctic Univ Norway, Dept Community Med, Fac Hlth Sci, Tromso, Norway, [Enget, T.] Univ Tromso, Arctic Univ Norway, Dept Community Med, Fac Hlth Sci, Tromso, Norway, [Skeie, G.] Univ Tromso, Arctic Univ Norway, Dept Community Med, Fac Hlth Sci, Tromso, Norway, [Weiderpass, E.] Inst Populat Based Canc Res, Canc Registry Norway, Dept Res, Oslo, Norway, [Weiderpass, E.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden, [Weiderpass, E.] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland, [Rostgaard-Hansen, A. L.] Danish Canc Soc Res Ctr, Copenhagen, Denmark, [Tjonneland, A.] Danish Canc Soc Res Ctr, Copenhagen, Denmark, [Affret, A.] Univ Paris Sud, Univ Paris Saclay, UVSQ, CESP,INSERM, Villejuif, France, [Boutron-Ruault, M. C.] Univ Paris Sud, Univ Paris Saclay, UVSQ, CESP,INSERM, Villejuif, France, [Fagherazzi, G.] Univ Paris Sud, Univ Paris Saclay, UVSQ, CESP,INSERM, Villejuif, France, [Affret, A.] Gustave Roussy, Villejuif, France, [Boutron-Ruault, M. C.] Gustave Roussy, Villejuif, France, [Fagherazzi, G.] Gustave Roussy, Villejuif, France, [Katzke, V.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Kuehn, T.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany, [Naska, A.] Hellen Hlth Fdn, Athens, Greece, [Orfanos, P.] Hellen Hlth Fdn, Athens, Greece, [Trichopoulou, A.] Hellen Hlth Fdn, Athens, Greece, [Naska, A.] Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Med Sch, Athens, Greece, [Orfanos, P.] Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Med Sch, Athens, Greece, [Trichopoulou, A.] Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat,Med Sch, Athens, Greece, [Pala, V.] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Epidemiol & Prevent Unit, Milan, Italy, [Palli, D.] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy, [Ricceri, F.] Reg Hlth Serv ASL TO3, Unit Epidemiol, Grugliasco, TO, Italy, [Ricceri, F.] Univ Turin, Dept Med Sci, Unit Canc Epidemiol, Turin, Italy, [de Magistris, M. Santucci] AOU Federico II, Naples, Italy, [Tumino, R.] ASP Ragusa, Civ MP Arezzo Hosp, Canc Registry & Histopathol Unit, Ragusa, Italy, [Engeset, D.] Norwegian Food Safety Author, Head Off, Oslo, Norway, [Barricarte, A.] Navarra Publ Hlth Inst, Pamplona, Spain, [Barricarte, A.] Navarra Inst Hlth Res IdiSNA, Pamplona, Spain, [Barricarte, A.] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, M. D.] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Amiano, P.] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Sanchez, M. J.] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain, [Chirlaque, M. D.] IMIB Arrixaca, Reg Hlth Council, Dept Epidemiol, Murcia, Spain, [Chirlaque, M. D.] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain, [Amiano, P.] BioDonostia Res Inst, Publ Hlth Div Gipuzkoa, San Sebastian, Spain, [Quiros, J. R.] Publ Hlth Directorate, Asturias, Spain, [Sanchez, M. J.] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain, [Dias, J. A.] Lund Univ, Dept Clin Sci Malmo, Lund, Sweden, [Drake, I.] Lund Univ, Dept Clin Sci Malmo, Lund, Sweden, [Boer, J. M. A.] Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands, [Ocke, M. C.] Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands, [Verschuren, W. M. M.] Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands, [Verschuren, W. M. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands, [Lassale, C.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Riboli, E.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Ward, H.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England, [Perez-Cornago, A.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England, European Commission (DG-SANCO), International Agency for Research on Cancer, Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia, Navarra, ISCIII RETIC (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, MRC, and National Institute for Health Research

Subjects
0301 basic medicine, Gerontology, Male, Cross-sectional study, Calibration (statistics), Medicine (miscellaneous), EPIC, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, Intake occasion, Feeding behavior, Medicine, Prospective Studies, Dietary-intake, Prospective cohort study, Meals, Meal patterns, Nutrition and Dietetics, 11 Medical And Health Sciences, Middle Aged, Research Papers, Nutrient intake, European Prospective Investigation into Cancer and Nutrition, Europe, Snacking, Female, 24 h dietary recall, Energy intake, Intake frequency, Snacks, Standardization, Adult, Aged, Cross-Sectional Studies, Energy Intake, Humans, Diet, Diet Surveys, Feeding Behavior, Cutoff, Population, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, 03 medical and health sciences, Environmental health, 030109 nutrition & dietetics, Nutrition & Dietetics, business.industry, Public Health, Environmental and Occupational Health, Frequency, Overweight, Recalls, Weight-loss, Energy-intake, business
Abstract

ObjectiveTo characterize meal patterns across ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.DesignCross-sectional study utilizing dietary data collected through a standardized 24 h diet recall during 1995–2000. Eleven predefined intake occasions across a 24 h period were assessed during the interview. In the present descriptive report, meal patterns were analysed in terms of daily number of intake occasions, the proportion reporting each intake occasion and the energy contributions from each intake occasion.SettingTwenty-seven centres across ten European countries.SubjectsWomen (64 %) and men (36 %) aged 35–74 years (n 36 020).ResultsPronounced differences in meal patterns emerged both across centres within the same country and across different countries, with a trend for fewer intake occasions per day in Mediterranean countries compared with central and northern Europe. Differences were also found for daily energy intake provided by lunch, with 38–43 % for women and 41–45 % for men within Mediterranean countries compared with 16–27 % for women and 20–26 % for men in central and northern European countries. Likewise, a south–north gradient was found for daily energy intake from snacks, with 13–20 % (women) and 10–17 % (men) in Mediterranean countries compared with 24–34 % (women) and 23–35 % (men) in central/northern Europe.ConclusionsWe found distinct differences in meal patterns with marked diversity for intake frequency and lunch and snack consumption between Mediterranean and central/northern European countries. Monitoring of meal patterns across various cultures and populations could provide critical context to the research efforts to characterize relationships between dietary intake and health.

Published
2016

44. Association of plasma phospholipid n-3 and n-6 polyunsaturated fatty acids with type 2 diabetes: The EPIC-InterAct case-cohort study

Author

Forouhi, N, Imamura, F, Sharp, S, Koulman, A, Schulze, M, Zheng, J, Ye, Z, Sluijs, I, Guevara, M, Huerta, J, Kröger, J, Wang, L, Summerhill, K, Griffin, J, Feskens, E, Affret, A, Amiano, P, Boeing, H, Dow, C, Fagherazzi, G, Franks, P, Gonzalez, C, Kaaks, R, Key, T, Khaw, K, Kühn, T, Mortensen, L, Nilsson, P, Overvad, K, Pala, V, Palli, D, Panico, S, Quirós, J, Rodriguez-Barranco, M, Rolandsson, O, Sacerdote, C, Scalbert, A, Slimani, N, Spijkerman, A, Tjonneland, A, Tormo, M, Tumino, R, van der A, D, van der Schouw, Y, Langenberg, C, Riboli, E, Wareham, N, Forouhi, Nita G, Imamura, Fumiaki, Sharp, Stephen J, Koulman, Albert, Schulze, Matthias B, Zheng, Jusheng, Ye, Zheng, Sluijs, Ivonne, Guevara, Marcela, Huerta, José María, Kröger, Janine, Wang, Laura Yun, Summerhill, Keith, Griffin, Julian L, Feskens, Edith J. M, Affret, Aurélie, Amiano, Pilar, Boeing, Heiner, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Gonzalez, Carlo, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Kühn, Tilman, Mortensen, Lotte Maxild, Nilsson, Peter M, Overvad, Kim, Pala, Valeria, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rodriguez Barranco, Miguel, Rolandsson, Olov, Sacerdote, Carlotta, Scalbert, Augustin, Slimani, Nadia, Spijkerman, Annemieke M. W, Tjonneland, Anne, Tormo, Maria Jose, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, Wareham, Nicholas J., Apollo - University of Cambridge Repository, [Forouhi,NG, Imamura,F, Sharp,SJ, Zheng,J, Ye,Z, Langenberg,C, Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. [Koulman,A, Wang,LY, Summerhill,K, Griffin,JL] MRC Human Nutrition Research, Cambridge, UK. [Schulze,MB, Kröger,J, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Sluijs,I, van der Schouw,YT] University Medical Center Utrecht, Utrecht, the Netherlands. [Guevara,M] Navarre Public Health Institute (ISPN), Pamplona, Spain. [Guevara,M, Huerta,JM, Amiano,P, Rodriguez-Barranco,M, Tormo,M] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Huerta,M, Tormo,M] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Feskens,EJM] Wageningen University, The Netherlands. [Affret,A, Dow,C, Fagherazzi,G] Inserm, CESP, U1018, Villejuif, France. Univ Paris-Sud, Villejuif, France, Gustave Roussy Institute, Villejuif, France. [Amiano,P] Public Health Division of Gipuzkoa, San Sebastian, Spain. Instituto BIO-Donostia, Basque Government, San Sebastian, Spain. [Boeing,H] German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Franks,PW, Nilsson,PM] Lund University, Malmö, Sweden. [Franks,PW, Rolandsson,O] Umeå University, Umeå, Sweden. [Gonzalez,C] Catalan Institute of Oncology (ICO), Barcelona, Spain. [Kaaks,R, Kühn1,T] German Cancer Research Centre (DKFZ), Heidelberg, Germany. [Key1,TJ] University of Oxford, Oxford, United Kingdom. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Mortensen,M] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Mortensen,M, Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Overvad,K] Aalborg University Hospital, Aalborg, Denmark. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Palli,D] Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Rodriguez-Barranco,M] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sacerdote,C] Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy. Human Genetics Foundation (HuGeF), Turin, Italy. [Scalbert,A, Slimani,N] International Agency for Research on Cancer, Lyon, France. [Spijkerman,AMW, van der A,DL] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Tjonneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tormo,MJ] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Tumino,R] Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy. [Riboli,E] School of Public Health, Imperial College London, London, United Kingdom., Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197)., Imamura, Fumiaki [0000-0002-6841-8396], Sharp, Stephen J [0000-0003-2375-1440], Koulman, Albert [0000-0001-9998-051X], Sluijs, Ivonne [0000-0001-7758-4911], Guevara, Marcela [0000-0001-9242-6364], Huerta, José María [0000-0002-9637-3869], Rodriguez-Barranco, Miguel [0000-0002-9972-9779], Tormo, Maria-Jose [0000-0003-1474-5233], van der Schouw, Yvonne T [0000-0002-4605-435X], Langenberg, Claudia [0000-0002-5017-7344], and Wareham, Nicholas J [0000-0003-1422-2993]

Subjects
Male, Physiology, Social Sciences, Diabetes Mellitus Tipo 2, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6::Linoleic Acids [Medical Subject Headings], Anatomy::Fluids and Secretions::Body Fluids::Blood::Plasma [Medical Subject Headings], Biochemistry, Plasma, Mathematical and Statistical Techniques, Endocrinology, Sociology, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Plant Products, Estudios prospectivos, Medicine and Health Sciences, Fosfolípidos, Ácidos grasos omega 3, Phospholipids, Medicine(all), Schools, Fatty Acids, Geographicals::Geographic Locations::Europe [Medical Subject Headings], food and beverages, Agriculture, Ácido eicosapentaenoico, 11 Medical And Health Sciences, Hematology, Middle Aged, Lipids, Type 2 Diabetes, Body Fluids, Blood, Ácidos Grasos Omega-6, Ácido 8,11,14-eicosanoico, Endokrinologi och diabetes, Physical Sciences, Fatty Acids, Unsaturated, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Medicine, Dieta, lipids (amino acids, peptides, and proteins), Anatomy, Europa, Statistics (Mathematics), Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids [Medical Subject Headings], Research Article, Cromatografía de gases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Endocrine Disorders, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Eicosanoids::8,11,14-Eicosatrienoic Acid [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Endocrinology and Diabetes, Research and Analysis Methods, Vegetable Oils, Blood Plasma, Education, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Docosahexaenoic Acids [Medical Subject Headings], General & Internal Medicine, Fatty Acids, Omega-6, Fatty Acids, Omega-3, Ácidos docosahexaenoicos, Diabetes Mellitus, Journal Article, Humans, Statistical Methods, Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], Ácido araquidónico, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Chromatography::Chromatography, Gas [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6 [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Eicosapentaenoic Acid [Medical Subject Headings], Ácidos Grasos Insaturados, Biology and Life Sciences, Ácido linoleico, Agronomy, Diabetes Mellitus, Type 2, Metabolic Disorders, Case-Control Studies, Oils, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated [Medical Subject Headings], Mathematics, Meta-Analysis, Crop Science
Abstract

Background Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class., Using a large European cohort, Nita Forouhi and colleagues investigate the association between the concentration of polyunsaturated fatty acids measured in plasma and risk of developing type 2 diabetes., Author Summary Why Was This Study Done? Most dietary guidelines recommend the consumption of polyunsaturated fatty acids for cardiovascular health, but it is unclear whether or how n-3 and n-6 types of polyunsaturated fatty acids are related to type 2 diabetes. Health concerns have been raised previously about a diet high in linoleic acid (n-6 fatty acid), but its association with type 2 diabetes is unclear. Major limitations in previous studies have included the error-prone subjective assessment of the habitual consumption of polyunsaturated fatty acids when dietary intakes were evaluated and a small number of type 2 diabetes cases (n = 71 to 673) when objective biomarkers of polyunsaturated fatty acids were measured. What Did the Researchers Do and Find? We measured circulating individual polyunsaturated fatty acids in the blood samples of individuals within a large study from across eight countries of Europe among a reference sample of 15,919 individuals as well as 12,132 individuals who subsequently developed diabetes. Individuals were followed up for an average of approximately 10 y. We investigated the association between individual polyunsaturated fatty acids and the risk of future type 2 diabetes using statistical analyses that accounted for factors that could be potential alternative explanations for any observed associations. We found that higher levels of blood alpha-linolenic acid, a plant-origin n-3 fatty acid, and n-6 linoleic acid, the most abundant type of polyunsaturated fatty acid, were associated with a lower risk of future type 2 diabetes. In contrast, higher levels of four other minor individual n-6 fatty acids were associated with higher type 2 diabetes risk, while the blood marine-origin n-3 fatty acids were not associated with future diabetes. What Do These Findings Mean? Our findings show that it is important to consider individual circulating polyunsaturated fatty acids for association with type 2 diabetes risk, rather than placing emphasis on the class of circulating polyunsaturated fatty acids. We found that blood n-6 linoleic acid, the most abundant polyunsaturated fatty acid, is inversely associated with type 2 diabetes. We found no evidence that blood total n-6 polyunsaturated fatty acids may elevate the risk of type 2 diabetes, but several individual minor blood n-6 polyunsaturated fatty acids were associated with increased type 2 diabetes risk, highlighting the importance of polyunsaturated fatty acid metabolism in the development of type 2 diabetes.

Published
2016
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45. Trends in socioeconomic inequalities in mortality in small areas of 33 Spanish cities

Author

Andreu Nolasco, Felicitas Domínguez-Berjón, Ana Gandarillas, Maica Rodríguez-Sanz, Montse Calvo, Mercè Gotsens, Mónica Ballesta, Lluís Cirera, Conchi Moreno-Iribas, Diego Salmerón, Carmen Martos, Antonio Daponte, Marc Marí-Dell’Olmo, Laia Palència, Natividad Izco Goñi, Margarita Taracido, Carme Borrell, Miguel A. Martinez-Beneito, [Marí-Dell’Olmo,M, Gotsens,M, Palència,L, Rodríguez-Sanz,M, Martinez-Beneito,MA, Ballesta,M, Cirera,L, Daponte,A, Salmerón,D, Taracido,M, Borrell,C] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Marí-Dell’Olmo,M, Borrell,C] Agència de Salut Pública de Barcelona, Barcelona, Spain. [Marí-Dell’Olmo,M, Borrell,C] Institut d’Investigació Biomèdica (IIB Sant Pau), Barcelona, Spain. [Marí-Dell’Olmo,M] Universitat Rovira i Virgili, Tarragona, Spain. [Martinez-Beneito,MA] Fundación para el fomento de la investigación sanitaria y biomédica de la Comunidad Valenciana (FISABIO), Valencia, Spain. [Ballesta,M, Salmerón,D] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Calvo,M] Estudios e investigación Sanitaria, Departamento de Sanidad y Consumo, Gobierno Vasco, Vitoria-Gasteiz, Spain. [Daponte,A] Observatorio de Salud y Medio Ambiente de Andalucía (OSMAN), Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Domínguez-Berjón,F, Gandarillas,A] Subdirección de Promoción de la Salud y Prevención, Consejería de Sanidad, Comunidad de Madrid, Spain. [Izco Goñi,N] Registro de Mortalidad, Consejería de Salud y Servicios Sociales, La Rioja, Spain. [Martos,C] Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain. [Moreno-Iribas,C] Instituto de Salud Pública de Navarra, Departamento de Salud, Gobierno de Navarra, Pamplona, Navarra, Spain. [Nolasco,A] Unidad de Investigación en Análisis de la Mortalidad y Estadísticas Sanitarias, Universidad de Alicante, San Vicente del Raspeig, Spain. [Taracido,M] Departamento de Medicina Preventiva y Salud Pública, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. [Borrell,C] Universitat Pompeu Fabra, Barcelona, Spain., This article was partially funded by Plan Nacional de I + D + I 2008–2011 and Instituto de Salud Carlos III (ISCIII) –Subdirección General de Evaluación y Fomento de la Investigación- (Award numbers: PI081488, PI081978, PI080367, PI08/1017, PI080330, P08/0142, PI081785, PI080662, PI081713, PI081058, PI081340, PI080803, PI126/08), Fundación Canaria de Investigación Sanitaria FUNCIS 84/07 and by CIBER Epidemiología y Salud Pública (CIBERESP)., Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Universidad de Alicante. Departamento de Enfermería Comunitaria, Medicina Preventiva y Salud Pública e Historia de la Ciencia, and Grupo Balmis de Investigación en Salud Comunitaria e Historia de la Ciencia

Subjects
Male, España, Poison control, Inequalities in mortality, Ciudades, 0302 clinical medicine, Risk Factors, Medicine, Socioeconomic inequalities, 030212 general & internal medicine, Censos, Urban areas, Child, Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Aged, 80 and over, Geografía, lcsh:Public aspects of medicine, Mortality rate, Multilevel model, Factores socioeconómicos, Censuses, Middle Aged, Random effects model, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Child, Preschool, Disease mapping, Enfermería, Disciplines and Occupations::Social Sciences::Sociology::Socioeconomic Factors [Medical Subject Headings], Female, 0305 other medical science, Research Article, Adult, Bayesian methods, Adolescent, Multilevel analysis, Disciplines and Occupations::Social Sciences::Demography::Censuses [Medical Subject Headings], Geographical inequalities, 03 medical and health sciences, Young Adult, Environmental health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Bayes Theorem [Medical Subject Headings], Humans, Mortality, Cities, Phenomena and Processes::Biological Phenomena::Ecological and Environmental Phenomena::Environment::Cities [Medical Subject Headings], Socioeconomic status, Aged, Demography, 030505 public health, business.industry, Public Health, Environmental and Occupational Health, Infant, Newborn, Urban Health, Ecological study, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Infant, lcsh:RA1-1270, Bayes Theorem, Fixed effects model, Health Status Disparities, Small areas, Cross-Sectional Studies, Socioeconomic Factors, Disciplines and Occupations::Natural Science Disciplines::Earth Sciences::Geography [Medical Subject Headings], Spain, Biostatistics, Trends, business
Abstract

Background: In Spain, several ecological studies have analyzed trends in socioeconomic inequalities in mortality from all causes in urban areas over time. However, the results of these studies are quite heterogeneous finding, in general, that inequalities decreased, or remained stable. Therefore, the objectives of this study are: (1) to identify trends in geographical inequalities in all-cause mortality in the census tracts of 33 Spanish cities between the two periods 1996–1998 and 2005–2007; (2) to analyse trends in the relationship between these geographical inequalities and socioeconomic deprivation; and (3) to obtain an overall measure which summarises the relationship found in each one of the cities and to analyse its variation over time. Methods: Ecological study of trends with 2 cross-sectional cuts, corresponding to two periods of analysis: 1996– 1998 and 2005–2007. Units of analysis were census tracts of the 33 Spanish cities. A deprivation index calculated for each census tracts in all cities was included as a covariate. A Bayesian hierarchical model was used to estimate smoothed Standardized Mortality Ratios (sSMR) by each census tract and period. The geographical distribution of these sSMR was represented using maps of septiles. In addition, two different Bayesian hierarchical models were used to measure the association between all-cause mortality and the deprivation index in each city and period, and by sex: (1) including the association as a fixed effect for each city; (2) including the association as random effects. In both models the data spatial structure can be controlled within each city. The association in each city was measured using relative risks (RR) and their 95 % credible intervals (95 % CI). Results: For most cities and in both sexes, mortality rates decline over time. For women, the mortality and deprivation patterns are similar in the first period, while in the second they are different for most cities. For men, RRs remain stable over time in 29 cities, in 3 diminish and in 1 increase. For women, in 30 cities, a non-significant change over time in RR is observed. However, in 4 cities RR diminishes. In overall terms, inequalities decrease (with a probability of 0.9) in both men (RR = 1.13, 95 % CI = 1.12–1.15 in the 1st period; RR = 1.11, 95 % CI = 1.09–1.13 in the 2nd period) and women (RR = 1.07, 95 % CI = 1.05–1.08 in the 1st period; RR = 1.04, 95 % CI = 1.02–1.06 in the 2nd period). Conclusions: In the future, it is important to conduct further trend studies, allowing to monitoring trends in socioeconomic inequalities in mortality and to identify (among other things) temporal factors that may influence these inequalities This article was partially funded by Plan Nacional de I + D + I 2008–2011 and Instituto de Salud Carlos III (ISCIII) –Subdirección General de Evaluación y Fomento de la Investigación- (Award numbers: PI081488, PI081978, PI080367, PI08/1017, PI080330, P08/0142, PI081785, PI080662, PI081713, PI081058, PI081340, PI080803, PI126/08), Fundación Canaria de Investigación Sanitaria FUNCIS 84/07 and by CIBER Epidemiología y Salud Pública (CIBERESP) SI

Published
2016

46. Modifiable causes of premature death in middle-age in Western Europe : Results from the EPIC cohort study

Author

Marc J. Gunter, Ellen A. Struijk, Paul Brennan, Paolo Vineis, Christina Bamia, Guri Skeie, David C. Muller, M. Luisa Redondo, Cornelia Weikert, Salvatore Panico, Elena Molina-Portillo, Antonio Agudo, Rosario Tumino, Françoise Clavel, W M Monique Verschuren, Petra H.M. Peeters, Olle Melander, Jone M. Altzibar, Heiner Boeing, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Elisabete Weiderpass, Gunnar Engström, Malin Sund, Teresa Norat, Anne Tjønneland, Manuela M. Bergmann, Philippos Orfanos, Laureen Dartois, Nicholas J. Wareham, Mattias Johansson, Elio Riboli, Kuanrong Li, Kay-Tee Khaw, Neil Murphy, Eiliv Lund, Antonia Trichopoulou, Marie-Christine Boutron-Ruault, Domenico Palli, Rudolf Kaaks, Konstantinos K. Tsilidis, Lluís Cirera, Pietro Ferrari, Valeria Pala, Timothy J. Key, Kim Overvad, Eva Ardanaz, Muller, David C, Murphy, Neil, Johansson, Mattia, Ferrari, Pietro, Tsilidis, Konstantinos K, Boutron Ruault, Marie Christine, Clavel, Francoise, Dartois, Laureen, Li, Kuanrong, Kaaks, Rudolf, Weikert, Cornelia, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Overvad, Kim, Redondo, M. Luisa, Agudo, Antonio, Molina Portillo, Elena, Altzibar, Jone M, Cirera, Lluí, Ardanaz, Eva, Khaw, Kay Tee, Wareham, Nicholas J, Key, Timothy J, Travis, Ruth C, Bamia, Christina, Orfanos, Philippo, Trichopoulou, Antonia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Verschuren, W. M. Monique, Struijk, Ellen A, Peeters, Petra H, Engström, Gunnar, Melander, Olle, Sund, Malin, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Norat, Teresa, Gunter, Marc, Riboli, Elio, Brennan, Paul, [Muller,DC, Johansson,M, Ferrari,P, Brennan,P] International Agency for Research on Cancer, Lyon, France. [Murphy,N, Vineis,P, Bueno-de-Mesquita,HB, Peeters,PH, Norat,T, Gunter,M, Riboli,E] School of Public Health, Imperial College London, London, UK] [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Boutron-Ruault,M] Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Boutron-Ruault,M, Clavel,F, Dartois,L] Université Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L, Dartois,L] Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Li,K, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Weikert,C, Bergmann,M, Boeing,H] German Institute of Human Nutrition Potsdam-Rehbrücke (DifE), Nuthetal, Germany. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Redondo,ML] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Portillo,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Portillo,E, Altzibar,JM, Cirera,M, Ardanaz,E] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Altzibar,JM] Public Health Division of Gipuzkoa-BIODONOSTIA, Basque Regional Health Department, Donostia - San Sebastián, Spain. [Cirera, L] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA) Pamplona, Pamplona, Spain. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ, Travis,RC] Cancer Epidemiology Unit, University of Oxford, Oxford, UK. [Bamia,C, Orfanos,P, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M. P. Arezzo' Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB, Verschuren,WMM] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Verschuren,WMM, Struijk,EA, Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Engström,G] Department of Clinical Science, Malmö Lund University, Lund, Sweden. [Melander,O] Department of Clinical Sciences, Hypertension & Cardiovascular Disease, Clinical Research Centre, Malmö University Hospital, Malmö, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Skeie,G, Lund,E] The Arctic University of Norway, Tromsø, Norway., This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Générale de la Santé). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Nordic Centre of xcellence programme on Food, Nutrition and Health. (Norway), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 to EPIC-Oxford),Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom). The sponsors did not have any input into study design, study conduct, data collection, analysis, or interpretation nor did they influence the preparation, review, or approval of the manuscript., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
Gerontology, Male, 030204 cardiovascular system & hematology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Institut Gustave Roussy, 0302 clinical medicine, Risk Factors, Medicine, 030212 general & internal medicine, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Non-U.S. Gov't, media_common, Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Mortality, Premature [Medical Subject Headings], Research Support, Non-U.S. Gov't, Smoking, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, General Medicine, Middle Aged, Europe, Hypertension, Absolute risk, Modifiable risk factors, Mortality, Premature death, Attributable fraction, language, Female, Cohort study, Research Article, Adult, medicine.medical_specialty, Alcohol Drinking, media_common.quotation_subject, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Library science, Motor Activity, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, Danish, 03 medical and health sciences, Diseases::Cardiovascular Diseases::Vascular Diseases::Hypertension [Medical Subject Headings], Life Expectancy, Excellence, General & Internal Medicine, Journal Article, Humans, Obesity, Aged, business.industry, Mortality, Premature, Public health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Life Expectancy [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Waist-Hip Ratio [Medical Subject Headings], language.human_language, Cancer registry, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Mortalidad, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Life expectancy, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Welfare, Modifiable risk factor, Mortalidad prematura
Abstract

Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. Methods: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. Results: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31–32 %) and 14 % (95 % CI, 12–16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8–12 %) and high blood pressure (9 %; 95 % CI, 7–11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55–59 %), being 35 % (95 % CI, 32–37 %) among never smokers and 74 % (95 % CI, 73–75 %) among current smokers. Conclusions: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed., This work was supported by the French Social Affairs & Health Ministry, Department of Health (Direction Générale de la Santé). The work undertaken by David C Muller for this project was performed during the tenure of an IARC-Australia fellowship supported by Cancer Council Australia. Elio Riboli was supported by the Imperial College Biomedical Research Centre funded by the National Institute of Health Research of UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom). The sponsors did not have any input into study design, study conduct, data collection, analysis, or interpretation nor did they influence the preparation, review, or approval of the manuscript.

Published
2016

47. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

Author

Travis, Ruth, Appleby, Paul, Martin, Richard, Holly, Jeff M.P., Albanes, Demetrius, Black, Amanda, Bueno-De-Mesquita, H. Bas, Chan, June, Chen, Chu, Chirlaque, María-Dolores, Cook, Michael, Deschasaux, Mélanie, Donovan, Jenny, Ferrucci, Luigi, Galan, Pilar, Giles, Graham, Giovannucci, Edward, Gunter, Marc, Habel, Laurel, Hamdy, Freddie, Helzlsouer, Kathy, Hercberg, Serge, Hoover, Robert, Janssen, Joseph A.M.J.L., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loïc, Metter, E. Jeffrey, Mikami, Kazuya, Morris, Joan, Neal, David, Neuhouser, Marian, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth, Pollak, Michael, Price, Alison, Roobol, Monique, Schaefer, Catherine, Schenk, Jeannette, Severi, Gianluca, Stampfer, Meir, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine, Touvier, Mathilde, Wald, Nicholas, Weiss, Noel, Ziegler, Regina, Key, Timothy, Allen, Naomi, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), University of Melbourne, Harvard School of Public Health, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Kaiser Permanente, Nuffield (Nuffield), Mercy Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Hawai‘i [Mānoa] (UHM), Kyoto Prefectural University of Medicine [Kyoto, Japon], Queen Mary University of London (QMUL), University of Cambridge [UK] (CAM), Radiation Effects Research Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Cancer Prevention Research Unit, Department of Oncology, McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, University of Washington [Seattle], Cancer Epidemiology Centre, Cancer Council Victoria, Human Genetics Foundation (HuGeF), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Hokkaido University Hospital [Sapporo], University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Deschasaux-Tanguy, Mélanie

Subjects
Urologic Diseases, Male, Aging, Oncology and Carcinogenesis, Article, growth-factor-i, serum-insulin, Risk Factors, prevention trial, Humans, Oncology & Carcinogenesis, Insulin-Like Growth Factor I, factor axis, igfbp-3, Cancer, Aged, Prostate Cancer, hyperplasia, Prostatic Neoplasms, Middle Aged, susceptibility loci, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, factor-binding protein-2, Centre for Surgical Research, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, factor (igf)-i, diet, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.

Published
2016

48. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Author

María José Sánchez, Jennifer Ose, Antonia Trichopoulou, J. Ramón Quirós, Marc J. Gunter, Xavier Castellsagué, Carlotta Sacerdote, Inger T. Gram, H B As Bueno-de-Mesquita, Johanna Ekström, Ruth C. Travis, Joakim Dillner, Carmen Navarro, Silvia de Sanjosé, Annika Idahl, Renée T. Fortner, Domenico Palli, Noémie Travier, Amalia Mattiello, David Lindquist, Annika Steffen, Elisabete Weiderpass, Christian Munk, Kay-Tee Khaw, Aurelio Barricarte, Elio Riboli, Michael Pawlita, Petra H.M. Peeters, Valeria Pala, Eiliv Lund, Philippos Orfanos, Sabina Rinaldi, F. Xavier Bosch, Pagona Lagiou, Kim Overvad, Nerea Larrañaga, N. Margall, Sylvie Mesrine, Massimo Tommasino, Silvia Franceschi, Silvia Polidoro, Melissa A. Merritt, Tim Waterboer, Giovanna Masala, Agnès Fournier, Rosario Tumino, Esther Roura, Anne Tjønneland, Françoise Clavel-Chapelon, University Medical Center Utrecht, Imperial College Trust, [Roura,E, de Sanjosé,S, Bosch,FX, Castellsagué,X] Unit of Infections and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Roura,E, Sánchez,MJ, Navarro,C, Barricarte,A, Larrañaga,N, Castellsagué,X] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Travier,N] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Waterboer,T, Pawlita,M] Division of Molecular Diagnostics of Oncogenic Infections (F020), Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.[Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Weiderpass, Dillner,J] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E, Gram,IT, Lund,E] Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Margall,N] Microbiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain. [Dillner,J] Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Munk,C] Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. [Palli,D, Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute–ISPO, Florence, Italy. [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Mesrine,S, Fournier,A] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, Villejuif, France.Institut Gustave Roussy, Villejuif, France. [Fortne,RT, Ose,J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Steffen,A] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Lagiou,P, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, United States of America. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic—M.P. Arezzo' Hospital, Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, University of Turin, Turin, Italy. Centre for Cancer Epidemiology and Prevention (CPO Piemonte), Turin, Italy. [Polidoro,S] Human Genetics Foundation (HuGeF), Turin, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.[Bueno-de-Mesquita,HB, Merritt,MA, Gunter,MJ, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.[Quirós,JR] Public Health Directorate, Asturias, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Barricarte,A] Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Larrañaga,N] Public Health Division of Gipuzkoa, BIODonostia Research Institute, Basque Health Department, Bilbao, Spain. [Ekström,J] BBMRI.se Service Center for Southern Sweden, Lund University, Medicon Village, Lund, Sweden. [Lindquist,D] Department of Radiation Sciences, Umeå University, Umeå, Sweden. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Rinaldi,S, Tommasino,M, Franceschi,S] International Agency for Research on Cancer, Lyon, France., Funding: The work was partially supported by grants from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI08/1308, PI13/00053, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RD12/0036/0056, RD12/0036/0018, and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2005SGR00695, 2009SGR939 and 2009SGR126, 2014SGR1077, 2014SGR2016). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and the Catalan Institute of Oncology, La Caixa (BM 06-130), RTICC-RD06/10091 (Spain), Danish Cancer Society (Denmark), Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC) and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom), and Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway).

Subjects
Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ::Cervical Intraepithelial Neoplasia [Medical Subject Headings], Oncology, Replacement therapy, Pathology and Laboratory Medicine, Antibodies, Viral, Biochemistry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pregnancy, Prospective Studies, lcsh:Science, Gonadal Steroid Hormones, education.field_of_study, Hormonal Therapy, Contraceptives, Humanos, Anticonceptivos, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Cohort studies, Science & Technology - Other Topics, Intreaepithelial neoplasia, Human, Cohort study, Oral, Human Papillomavirus Infection, medicine.medical_specialty, Càncer de coll uterí, Sexually Transmitted Diseases, Estudios retrospectivos, 03 medical and health sciences, Drug Therapy, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Uterine Cervical Neoplasms [Medical Subject Headings], Neoplasias del cuello uterino, Humans, education, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Parity [Medical Subject Headings], Aged, Pharmacology, Gynecology, Cancer och onkologi, Science & Technology, Herpes Genitalis, Genitourinary Infections, Herpesvirus 2, lcsh:R, Case-control study, Biology and Life Sciences, Estrogens, medicine.disease, Hormones, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, Case-Control Studies, Cervical cancer, Medical Devices and Equipment, lcsh:Q, Intrauterine Devices, 0301 basic medicine, Glutathione-S-transferase, Viral Diseases, Human papillomavirus infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Herpesvirus 2, Human, lcsh:Medicine, Uterine Cervical Neoplasms, Chlamydia trachomatis, Cervical Cancer, Cohort Studies, Cervix cancer, Paridad, Medicine and Health Sciences, Viral, Non-U.S. Gov't, Prospective cohort study, Papillomaviridae, Reproductive History, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Reproductive Control Agents::Contraceptive Agents [Medical Subject Headings], Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Pharmaceutics, Research Support, Non-U.S. Gov't, Femenino, Drugs, Estudios de Casos y Controles, Middle Aged, humanities, Multidisciplinary Sciences, Infectious Diseases, Serology, Research Design, Hormonal therapy, Female, Research Article, Biotechnology, Adult, Risk, Papillomaviruses, Embarazo, General Science & Technology, Hormone Replacement Therapy, Urology, Population, Individual data, Research Support, Research and Analysis Methods, Cervical intraepithelial neoplasia, Antibodies, Contraceptives, Oral, Hormonal, Young Adult, Collaborative reanalysis, Internal medicine, Oral-contraceptives, MD Multidisciplinary, Journal Article, medicine, Multicentric case-control, Cervical Intraepithelial Neoplasia, Neoplasia Intraepitelial Cervical, Papil·lomavirus, Reproductive factors, Hormonal, business.industry, Carcinoma, Papillomavirus Infections, Cancers and Neoplasms, Chlamydia Infections, Uterine Cervical Dysplasia, Squamous Cell, Organisms::Viruses::DNA Viruses::Papillomaviridae [Medical Subject Headings], business, Gynecological Tumors, Follow-Up Studies
Abstract

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health (Exp P10710130) In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.

Published
2016

49. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Author

Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] INSERM, Centre for Research in Epidemiology and Population Health (CESP), nutrition, Hormones and Women’s Health Team, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford

Subjects
Oncology, Male, Neoplasias Hepáticas, Cirrhosis, Magnetic Resonance Spectroscopy, Epidemiology, Hepatocellular carcinoma, Nuclear magnetic resonance, Cohort Studies, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, CIRRHOSIS, Early Detection of Cancer, Medicine(all), 0303 health sciences, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Liver Neoplasms, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], Metabolómica, Estudios Prospectivos, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Liver Neoplasm, 030220 oncology & carcinogenesis, Female, Liver cancer, Case-Control Studie, Life Sciences & Biomedicine, Metabolomics, Carcinoma Hepatocelular, Research Article, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], TISSUE METABOLOMICS, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Metabolomic, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings], Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, IDENTIFY SERUM BIOMARKERS, Internal medicine, General & Internal Medicine, medicine, Humans, Obesity, Epidemiologia, 030304 developmental biology, FATTY LIVER-DISEASE, Aged, Hepatitis, Science & Technology, business.industry, Case-control study, METABONOMICS, Cancer, MASS-SPECTROMETRY, medicine.disease, NMR, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Case-Control Studies, DISCOVERY, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Immunology, RISK-FACTORS, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).

Published
2015

50. Prognostic role of pre-diagnostic circulating inflammatory biomarkers in breast cancer survival: evidence from the EPIC cohort study.

Author

Castro-Espin C, Cairat M, Navionis AS, Dahm CC, Antoniussen CS, Tjønneland A, Mellemkjær L, Mancini FR, Hajji-Louati M, Severi G, Le Cornet C, Kaaks R, Schulze MB, Masala G, Agnoli C, Sacerdote C, Crous-Bou M, Sánchez MJ, Amiano P, Chirlaque MD, Guevara M, Smith-Byrne K, Heath AK, Christakoudi S, Gunter MJ, Rinaldi S, Agudo A, and Dossus L

Subjects
Humans, Female, Middle Aged, Prognosis, Aged, Postmenopause blood, Cohort Studies, Interleukin-10 blood, Adult, Tumor Necrosis Factor-alpha blood, Proportional Hazards Models, Breast Neoplasms mortality, Breast Neoplasms blood, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Inflammation blood, Inflammation mortality, Biomarkers, Tumor blood, Interleukin-6 blood
Abstract

Background: Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive., Methods: We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-cause and BC-specific mortality, adjusting for tumour characteristics and lifestyle factors., Results: Over a 7-year follow-up after diagnosis, 229 women died, 163 from BC. Elevated IL-6 levels were associated with increased all-cause mortality risk (HR 1-SD 1.25, 95% CI 1.07-1.47). Among postmenopausal, IL-6 was associated with higher all-cause (HR 1-SD 1.41, 95% CI 1.18-1.69) and BC-specific mortality (HR 1-SD 1.31, 95% CI 1.03-1.66), (P Heterogeneity (pre/postmenopausal)  < 0.05 for both), while IL-10 and TNFα were associated with all-cause mortality only (HR 1-SD 1.19, 95% CI 1.02-1.40 and HR 1-SD 1.28, 95% CI 1.06-1.56). Among ER+PR+, IL-10 was associated with all-cause and BC-specific mortality (HR 1-SD 1.35, 95% CI 1.10-1.65 and HR 1-SD 1.42 95% CI 1.08-1.86), while TNF-α was associated with all-cause mortality in HER2- (HR 1-SD 1.31, 95% CI 1.07-1.61). An inflammatory score predicted higher all-cause mortality, especially in postmenopausal women (HR 1-SD 1.30, 95% CI 1.07-1.58)., Conclusions: Higher pre-diagnosis IL-6 levels suggest poorer long-term survival among BC survivors. In postmenopausal survivors, elevated IL-6, IL-10, and TNFα and inflammatory scores seem to predict all-cause mortality., (© 2024. The Author(s).)

Published
2024
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