Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility.
EPIC
MAD2L1
diet
dietary fat
dietary sugar
epidemiology
gene-environment interaction
genetics
mouse model
pancreatic cancer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
14 07 2020
14 07 2020
Historique:
received:
18
11
2019
revised:
26
05
2020
accepted:
17
06
2020
entrez:
16
7
2020
pubmed:
16
7
2020
medline:
30
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32668252
pii: S2211-1247(20)30861-5
doi: 10.1016/j.celrep.2020.107880
pmc: PMC7370178
pii:
doi:
Substances chimiques
Dietary Carbohydrates
0
Dietary Fats
0
Dietary Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107880Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0427
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT205915/Z/17/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0428
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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