Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility
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 epid...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720308615 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
James Dooley Vasiliki Lagou Jermaine Goveia Anna Ulrich Katerina Rohlenova Nathalie Heirman Tobias Karakach Yulia Lampi Shawez Khan Jun Wang Tom Dresselaers Uwe Himmelreich Marc J. Gunter Inga Prokopenko Peter Carmeliet Adrian Liston |
| spellingShingle |
James Dooley Vasiliki Lagou Jermaine Goveia Anna Ulrich Katerina Rohlenova Nathalie Heirman Tobias Karakach Yulia Lampi Shawez Khan Jun Wang Tom Dresselaers Uwe Himmelreich Marc J. Gunter Inga Prokopenko Peter Carmeliet Adrian Liston Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility Cell Reports pancreatic cancer diet genetics dietary sugar dietary fat mouse model |
| author_facet |
James Dooley Vasiliki Lagou Jermaine Goveia Anna Ulrich Katerina Rohlenova Nathalie Heirman Tobias Karakach Yulia Lampi Shawez Khan Jun Wang Tom Dresselaers Uwe Himmelreich Marc J. Gunter Inga Prokopenko Peter Carmeliet Adrian Liston |
| author_sort |
James Dooley |
| title |
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_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_sort |
heterogeneous effects of calorie content and nutritional components underlie dietary influence on pancreatic cancer susceptibility |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-07-01 |
| description |
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. |
| topic |
pancreatic cancer diet genetics dietary sugar dietary fat mouse model |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720308615 |
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doaj-575ffb0ba48a4cca8912c3a6e88a02962020-11-25T02:54:40ZengElsevierCell Reports2211-12472020-07-01322107880Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer SusceptibilityJames Dooley0Vasiliki Lagou1Jermaine Goveia2Anna Ulrich3Katerina Rohlenova4Nathalie Heirman5Tobias Karakach6Yulia Lampi7Shawez Khan8Jun Wang9Tom Dresselaers10Uwe Himmelreich11Marc J. Gunter12Inga Prokopenko13Peter Carmeliet14Adrian Liston15Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, BelgiumVIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, BelgiumLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven 3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven-University of Leuven, Leuven 3000, BelgiumDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7XH, UKLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven 3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven-University of Leuven, Leuven 3000, BelgiumVIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, BelgiumBioinformatics Core Laboratory, Children’s Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada; Rady Faculty of Health Sciences, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3T 2N2, CanadaVIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, BelgiumLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven 3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven-University of Leuven, Leuven 3000, BelgiumCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Science, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Imaging and Pathology, KU Leuven-University of Leuven, Leuven 3000, BelgiumDepartment of Imaging and Pathology, KU Leuven-University of Leuven, Leuven 3000, BelgiumSection of Nutrition and Metabolism, International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, FranceDepartment of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK; UMR 8199 - EGID, Institut Pasteur de Lille, CNRS, University of Lille, 59000 Lille, France; Section of Genetics and Genomics, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London SW7 2AZ, UK; Corresponding authorLaboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology, VIB, Leuven 3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven-University of Leuven, Leuven 3000, Belgium; Corresponding authorLaboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720308615pancreatic cancerdietgeneticsdietary sugardietary fatmouse model |