Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility

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

Cell Reports (Jul 2020)

Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility

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

Affiliations

James Dooley: Laboratory 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
Vasiliki Lagou: VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium
Jermaine Goveia: Laboratory 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
Anna Ulrich: Department of Clinical & Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK
Katerina Rohlenova: Laboratory 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
Nathalie Heirman: VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium
Tobias Karakach: Bioinformatics 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, Canada
Yulia Lampi: VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium
Shawez Khan: Laboratory 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
Jun Wang: CAS 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, China
Tom Dresselaers: Department of Imaging and Pathology, KU Leuven-University of Leuven, Leuven 3000, Belgium
Uwe Himmelreich: Department of Imaging and Pathology, KU Leuven-University of Leuven, Leuven 3000, Belgium
Marc J. Gunter: Section of Nutrition and Metabolism, International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France
Inga Prokopenko: Department 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 author
Peter Carmeliet: Laboratory 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 author
Adrian Liston: Laboratory 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 author

Journal volume & issue: Vol. 32, no. 2
p. 107880

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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