Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility
Autor: | Vasiliki Lagou, Uwe Himmelreich, Nathalie Heirman, Adrian Liston, Yulia Lampi, Peter Carmeliet, Anna Ulrich, Shawez Khan, Inga Prokopenko, Jermaine Goveia, James Dooley, Jun Wang, Katerina Rohlenova, Marc J. Gunter, Tobias K. Karakach, Tom Dresselaers |
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Přispěvatelé: | CCSD, Accord Elsevier, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Surrey (UNIS), University of Manitoba [Winnipeg], University of Chinese Academy of Sciences [Beijing] (UCAS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), 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 National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Imperial College London, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male MAD2L1 Calorie [SDV]Life Sciences [q-bio] pancreatic cancer PROTEIN Type 2 diabetes Bioinformatics 0302 clinical medicine Epidemiology Nutritional Physiological Phenomena AMINO-ACIDS genetics lcsh:QH301-705.5 RISK education.field_of_study Cell Cycle Middle Aged METABOLIC REQUIREMENTS 3. Good health [SDV] Life Sciences [q-bio] dietary fat Female epidemiology Dietary Proteins Disease Susceptibility Life Sciences & Biomedicine EXPRESSION medicine.medical_specialty mouse model Population General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Diabetes mellitus Pancreatic cancer medicine Dietary Carbohydrates Animals Humans dietary sugar Obesity GENOME-WIDE ASSOCIATION education Aged Science & Technology business.industry Cancer ADENOCARCINOMA CONSUMPTION Cell Biology MASS-SPECTROMETRY medicine.disease Dietary Fats GENE gene-environment interaction Mice Inbred C57BL Pancreatic Neoplasms 030104 developmental biology lcsh:Biology (General) business Energy Intake EPIC diet 030217 neurology & neurosurgery |
Zdroj: | Cell Reports Cell Reports, 2020, 32, pp.107880-. ⟨10.1016/j.celrep.2020.107880⟩ Cell Reports, Vol 32, Iss 2, Pp 107880-(2020) Cell Reports, Elsevier Inc, 2020, 32, pp.107880-. ⟨10.1016/j.celrep.2020.107880⟩ |
ISSN: | 2211-1247 |
Popis: | Summary Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. Known risk factors include obesity, diet, and type 2 diabetes; however, the low incidence rate and interconnection of these factors confound the isolation of individual effects. Here, we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the effects of obesity, diet, and diabetes on pancreatic cancer. Through longitudinal monitoring and multi-omics analysis in mice, we found distinct effects of protein, sugar, and fat dietary components, with dietary sugars increasing Mad2l1 expression and tumor proliferation. Using epidemiological approaches in humans, we find that dietary sugars give a MAD2L1 genotype-dependent increased susceptibility to pancreatic cancer. The translation of these results to a clinical setting could aid in the identification of the at-risk population for screening and potentially harness dietary modification as a therapeutic measure. Graphical Abstract Highlights • Distinct roles for dietary fat, protein, and sugar on murine pancreatic cancer • Dietary glucose triggers Mad2l1 upregulation and tumor cell proliferation in mice • Gene-diet interaction identifies sugar-MAD2L1 link in human pancreatic cancer • Dietary plant fats were protective in human pancreatic cancer susceptibility Dooley et al. used parallel analysis of a murine pancreatic cancer model and a human prospective cohort to study the interaction of diet and pancreatic cancer. Both systems identify complex effects with different dietary components, converging on a link between dietary sugar and the cell-cycle checkpoint gene MAD2L1. |
Databáze: | OpenAIRE |
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