In some individuals, a diet high in sugar increases the likelihood of developing pancreatic cancer and also drives the aggressive growth of tumours, a study by researchers from the Babraham Institute, Cambridge, UK, and VIB-KU Leuven, Belgium, has found.
The researchers completed a comprehensive project using experimental work in mice and human data, including from pancreatic cancer patients, to understand the influence of different dietary components on the development and progression of pancreatic cancer. The research is published today in the journal Cell Reports. Pancreatic cancer is a rare but fatal form of cancer, due to late detection and a poor understanding of the risk factors. Known risk factors include obesity, diet and type 2 diabetes, however the low incidence rate and interconnection of these factors mean that it is difficult to tease apart their individual contribution.
The researchers first studied the effects of obesity, diet and diabetes on pancreatic cancer development, growth and lethality in mice. In parallel they analysed the effect of diet using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which followed over half a million Europeans for 20 years.
The researchers found that obesity, diet and diabetes had profound and differing impacts on cancer incidence and growth. Using mice, the results indicated that obesity, dietary animal fats and dietary sugar were independent drivers of different facets of pancreatic cancer progression. In particular the results shed light on how pancreatic cancer might be affected by dietary sugar, with more rapid tumour growth and escalated lethality.
The effect of dietary sugars on pancreatic cancer development was preserved between mice and humans. In 500 study participants with pancreatic cancer, the researchers explored the interaction between genes and diet and found that high levels of dietary sugar increased pancreatic cancer risk in individuals with a certain genetic variation (found in 6% of the population).
Dr James Dooley, senior staff scientist in the Immunology programme at the Babraham Institute, said: "Our study raises concern about the remarkable toxicity of sugar in our diet. We spent years looking at different dietary and genetic changes, and nothing has anywhere near the detrimental impact of a high sugar diet. Our findings suggest that it drives pancreatic cancer onset and makes it a more aggressive and lethal tumour."
Analysis of the human-derived data from the large EPIC study suggested that dietary plant fats reduced the risk of pancreatic cancer, estimating a 10% decrease in risk when eating the equivalent of an avocado a day.
Professor Adrian Liston, senior group leader at the Babraham Institute, said: "This study shows the power of combining animal research with the study of patients. We were able to use epidemiology and large patient-based resources to find a link in humans, and then go back to an animal model to formally test the direction of causality. Finding the same gene-diet link in both mice and humans makes us confident that diet is modifying disease risk, and gives us the tools to test preventative and therapeutic interventions."
While the impact of nutrition on cancer development continues to be explored and debated, this study provides a vital foundation for further studies and important indications to explore. Armed with this knowledge, clinicians could be supported to identify individuals at increased risk for screening and individuals with a high-risk genetic background could take pro-active dietary changes to reduce their risk of pancreatic cancer.
Ali Stunt FRSA, Founder and Chief Executive of Pancreatic Cancer Action, concurs: "Here at Pancreatic Cancer Action, we strongly advocate for high quality research into this neglected cancer. Dr Liston and his team have made a major contribution into understanding how diet and genetics changes the risk for pancreatic cancer. Healthy lifestyle choices, such as avoiding sugar-sweetened beverages and choosing a diet rich in vegetables, can reduce your risk of pancreatic cancer, and may be especially important in families with a history of the disease."
Pancreatic cancer statistics (data from Cancer Research UK)
Dooley, J. et al.
Heterogeneous effects of calorie content and nutritional components underlie dietary influence over pancreatic cancer susceptibility in mice and humansCell Reports.
Dr Louisa Wood, Communications Manager, firstname.lastname@example.org
Professor Adrian Liston, Senior group leader, email@example.com
The image shows proliferating cells in a pancreatic tumour taken from a mouse on a high glucose diet. Green fluorescence is due to a marker (Ki67) for proliferating cells, red (CD31) shows blood vessels, blue (Dapi) shows the location of nuclei.
Academy of Medical Sciences labelling:
Affiliated authors (in author order):
Dr James Dooley, senior staff scientist, Liston labProfessor Adrian Liston, senior group leader, Immunology research programme
This work was supported by the VIB, the KU Leuven IUAP project (T-TIME), the Biotechnology and Biological Sciences Research Council through Institute Strategic Program Grant funding and a Core Capability Grant to the Babraham Institute.
Animal research statement
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The research presented here used mice that were housed at the University of Leuven and used in accordance with the University of Leuven Animal Ethics Committee. Genetically altered mice were used to separate the influence of obesity, diet and diabetes on the development of pancreatic cancer. The research used mice with mutations that drive the development of obesity and type 2 diabetes. It also used mice that had been genetically modified to promote the onset of pancreatic cancer. Mice were interbred and scanned regularly using Magnetic Resonance Imaging (MRI) for the presence and size of pancreatic tumours, and tissue samples were taken from the mice (after death) to analyse tumour and pancreatic tissue composition. Mice were monitored daily throughout their lives and were humanely killed once their tumours reached a defined size (for wellbeing purposes) or if they showed signs of distress. Please follow the link for further details of our animal research and our animal welfare practices. https://www.babraham.ac.uk/about-us/animal-research
About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation, immunology and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through Institute Strategic Programme Grants and an Institute Core Capability Grant, and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government. BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
VIB-KU Leuven Center for Brain & Disease Research
Scientists at the VIB-KU Leuven Center for Brain & Disease study how brain cells are organized and how they communicate with each other. These mechanisms reveal and provide insights into what goes wrong in brain diseases such as Alzheimer's, Parkinson's, ALS and dystonia. This basic work should ultimately lead to new drugs for use against these currently incurable diseases.
Basic research in life sciences is VIB’s raison d’être. VIB is an independent research institute where some 1,500 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information. More info can be found on www.vib.be
KU Leuven is a leading European university dedicated to research, education and service to society. It is a founding member of the League of European Research Universities (LERU) and has a strong European and international orientation. Its sizeable academic staff conducts basic and applied research in a comprehensive range of disciplines. University Hospitals Leuven, its network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research. The University welcomes more 50,000 students from over 140 countries. Its doctoral schools organise internationally oriented PhD programmes for over 4,500 doctoral students. More info: www.kuleuven.be/english
15 July 2020