Author Response: Identifying metabolic features of colorectal cancer liability using Mendelian randomization
Year: 2023
Type: peer-review
Abstract: Colorectal cancer, or bowel cancer, is the fourth most common cause of death from cancer worldwide. Understanding how the cancer develops and recognizing early signs is essential, as people who receive treatment early on have higher survival rates. One way to boost early detection and disease survival rates is through identifying early colorectal cancer biomarkers. For example, metabolites produced when cells process nutrients have been shown to play a role in the development of colon cancer. Certain metabolites could therefore serve as biomarkers, which can be detected in routine blood tests. But first, scientists need to identify the exact metabolic processes involved in cancer development. Bull, Hazelwood et al. show that fat metabolites during early adulthood may help predict colorectal cancer risk. In the experiments, the team assessed the link between an individual’s genetic risk for developing colorectal cancer and metabolites in their blood. By looking at data from over 6,000 individuals living in the UK, followed from early life into adulthood, they found higher fatty acid and low-density lipoprotein levels in young adults at risk of colorectal cancer. However, the results could not be replicated in a separate cohort study of middle-aged adults. Bull, Hazelwood et al. noted that many individuals in this older age group use fat-targeting drugs called statins, which may have obscured this connection. The study of Bull, Hazelwood et al. shows that colorectal cancer risk indicators may be present from adolescence to around 40 years, before most individuals are diagnosed. The results suggest this may be a window for early detection and preventive interventions. It also highlights that differences in fat metabolism, possibly linked to genetic differences, may underlie colorectal cancer risk. More studies are needed to better understand how and whether interventions targeting fat levels may help prevent colorectal cancer development.
Authors: Caroline Bull, Emma Hazelwood, Joshua A Bell, Vanessa Tan, Andrei-Emil Constantinescu, Carolina Borges, Danny Legge, Kimberley Burrows, Jeroen R Huyghe, Hermann Brenner, Sergi Castellvi-Bel, Andrew T Chan, Sun-Seog Kweon, Loic Le Marchand, Li Li, Iona Cheng, Rish K Pai, Jane C Figueiredo, Neil Murphy, Marc J Gunter, Nicholas J Timpson, Emma E Vincent
Institutions: University of Bristol, Fred Hutch Cancer Center, German Cancer Research Center, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Harvard University, Chonnam National University Hwasun Hospital, University of Hawaiʻi at Mānoa, University of Virginia, University of California, San Francisco, Mayo Clinic, University of Southern California, Centre international de recherche sur le cancer, Imperial College London
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Funders: U.S. Department of Health and Human Services, Univerzita Karlova v Praze, McGill University, Wellcome Trust, Swedish Cancer Foundation, Génome Québec, Centres de Recerca de Catalunya, Cancer Research UK, National Institute for Health and Care Research, Diabetes UK, University of Bristol, Grantová Agentura České Republiky, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Ministerstvo Zdravotnictví Ceské Republiky, Karolinska Institutet, Stockholms Läns Landsting, Vetenskapsrådet, Junta de Castilla y León, Xarxa de Bancs de Tumors de Catalunya, National Institutes of Health, Elizabeth Blackwell Institute for Health Research, University of Bristol, Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, Medical Research Council, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, National Heart, Lung, and Blood Institute, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: G1059998468, G1087756281, G1188670755, G1245744068, G1245747547, Discovery and verification of novel biomarkers of colorectal cancer recurrence, G1395687794, G1617166219, Institutional Strategic Support Fund, G1782702759, Transdisciplinary Studies of Genetic Variation in Colorectal Cancer, G1857775333, G1939941310, G220105922, G2209031392, G2294948847, Diet, Activity, and Lifestyle as a Risk Factor for Colorectal Cancer, G239036932, G2430800857, G2432069567, G2438974996, G2503663851, Verbundvorhaben: Verbesserung der Langzeitprognose und der Lebensqualität von Patienten mit kolorektalem Karzinom (IMPACT-Studie), Teilprojekte der Universität Heidelberg (Anschlussvorhaben), Verbundvorhaben: Verbesserung der Langzeitprognose und der Lebensqualität von Patienten mit kolorektalem Karzinom (IMPACT-Studie), Teilprojekte des DKFZ (Anschlussvorhaben), G2703516656, G2741775834, G3246171900, G3283741708, Verbundvorhaben: Verbesserung der Langzeitprognose und der Lebensqualität von Patienten mit kolorektalem Karzinom (IMPACT-Studie), Arbeitspaket Lebensqualität und Langzeitüberleben, Interdisciplinary studies of the determinants, impact and control of colorectal cancer. A genetic-epidemiological and population-based approach, G388930096, G4075560779, G4234380927, Ontario Registry for Studies of Familial Colon Cancer, G4276214582, G4341742837, G4431312015, Horizontal transfer of mitochondria in cancer biology, G4864901413, G50211877, Metabolomic Strategies for Discovery and Validation of Biomarkers of Colorectal Cancer Recurrence, Microbial metabolites and dietary factors influencing genome and epigenome in colorectal cancer development, Verbundprojekt: Verbesserung der Langzeitprognose und der Lebensqualität von Patienten mit kolorektalem Karzinom (IMPACT-Studie), Arbeitspaket Gewebemarker, G5429766098, G5590407248, G5788305929, G6054300366, G6058434148, Data mining epidemiological relationships: integration of causal analysis with published evidence, G7049171053, G7192512249, G7385817896, G7412051999, Genomic Wide Association Study of Colorectal Cancer, G7674072152, Data sharing: the Colon Cancer Family Registry Cohort, G804866679, G8173965379, G8205009473, G8237641289, G8502142660, Molecular Epidemiology of Colorectal Cancer, G8796559087, G8838857111, G889473840, G9000011662, G9000065182, G9000078665, G9000097779, G9000111169, G9000131309, G9000202936, G9000225879, G9000283142, G9000307519, Cancer Center Support Grant, Transdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare Study, G980164052, G993134884
OpenAlex ID: W4390049077