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
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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