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Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility
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 epidemiologic...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370178/ https://www.ncbi.nlm.nih.gov/pubmed/32668252 http://dx.doi.org/10.1016/j.celrep.2020.107880 |
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author | Dooley, James Lagou, Vasiliki Goveia, Jermaine Ulrich, Anna Rohlenova, Katerina Heirman, Nathalie Karakach, Tobias Lampi, Yulia Khan, Shawez Wang, Jun Dresselaers, Tom Himmelreich, Uwe Gunter, Marc J. Prokopenko, Inga Carmeliet, Peter Liston, Adrian |
author_facet | Dooley, James Lagou, Vasiliki Goveia, Jermaine Ulrich, Anna Rohlenova, Katerina Heirman, Nathalie Karakach, Tobias Lampi, Yulia Khan, Shawez Wang, Jun Dresselaers, Tom Himmelreich, Uwe Gunter, Marc J. Prokopenko, Inga Carmeliet, Peter Liston, Adrian |
author_sort | Dooley, James |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7370178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-73701782020-07-23 Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility Dooley, James Lagou, Vasiliki Goveia, Jermaine Ulrich, Anna Rohlenova, Katerina Heirman, Nathalie Karakach, Tobias Lampi, Yulia Khan, Shawez Wang, Jun Dresselaers, Tom Himmelreich, Uwe Gunter, Marc J. Prokopenko, Inga Carmeliet, Peter Liston, Adrian Cell Rep Article 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. Cell Press 2020-07-14 /pmc/articles/PMC7370178/ /pubmed/32668252 http://dx.doi.org/10.1016/j.celrep.2020.107880 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Dooley, James Lagou, Vasiliki Goveia, Jermaine Ulrich, Anna Rohlenova, Katerina Heirman, Nathalie Karakach, Tobias Lampi, Yulia Khan, Shawez Wang, Jun Dresselaers, Tom Himmelreich, Uwe Gunter, Marc J. Prokopenko, Inga Carmeliet, Peter Liston, Adrian Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title | Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title_full | Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title_fullStr | Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title_full_unstemmed | Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title_short | Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility |
title_sort | heterogeneous effects of calorie content and nutritional components underlie dietary influence on pancreatic cancer susceptibility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370178/ https://www.ncbi.nlm.nih.gov/pubmed/32668252 http://dx.doi.org/10.1016/j.celrep.2020.107880 |
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