Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort
Background: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, but if discovered at an early stage, the survival rate is high. The aim of this study was to identify novel markers predictive of future CRC risk using untargeted metabolomics. Methods: This study included pros...
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Umeå universitet, Institutionen för matematik och matematisk statistik
2023
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Online Access: | http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218144 https://doi.org/10.1186/s40170-023-00319-x |
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ftumeauniv:oai:DiVA.org:umu-218144 2024-02-04T10:03:19+01:00 Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort Vidman, Linda Zheng, Rui Bodén, Stina Ribbenstedt, Anton Gunter, Marc J. Palmqvist, Richard Harlid, Sophia Brunius, Carl van Guelpen, Bethany 2023 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218144 https://doi.org/10.1186/s40170-023-00319-x eng eng Umeå universitet, Institutionen för matematik och matematisk statistik Umeå universitet, Onkologi Umeå universitet, Pediatrik Umeå universitet, Patologi Umeå universitet, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM) Department of Surgical Sciences, Medical Epidemiology, Uppsala University, Uppsala, Sweden Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, Sweden Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK Cancer & Metabolism, 2023, 11:1, orcid:0000-0002-8958-975x orcid:0000-0002-9933-2843 orcid:0000-0001-8540-6891 orcid:0000-0002-9692-101X http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218144 doi:10.1186/s40170-023-00319-x PMID 37849011 ISI:001088049400001 info:eu-repo/semantics/openAccess Untargeted metabolomics Colorectal cancer Early detection Cancer and Oncology Cancer och onkologi Article in journal info:eu-repo/semantics/article text 2023 ftumeauniv https://doi.org/10.1186/s40170-023-00319-x 2024-01-10T23:36:28Z Background: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, but if discovered at an early stage, the survival rate is high. The aim of this study was to identify novel markers predictive of future CRC risk using untargeted metabolomics. Methods: This study included prospectively collected plasma samples from 902 CRC cases and 902 matched cancer-free control participants from the population-based Northern Sweden Health and Disease Study (NSHDS), which were obtained up to 26 years prior to CRC diagnosis. Using reverse-phase liquid chromatography-mass spectrometry (LC-MS), data comprising 5015 metabolic features were obtained. Conditional logistic regression was applied to identify potentially important metabolic features associated with CRC risk. In addition, we investigated if previously reported metabolite biomarkers of CRC risk could be validated in this study population. Results: In the univariable analysis, seven metabolic features were associated with CRC risk (using a false discovery rate cutoff of 0.25). Two of these could be annotated, one as pyroglutamic acid (odds ratio per one standard deviation increase = 0.79, 95% confidence interval, 0.70-0.89) and another as hydroxytigecycline (odds ratio per one standard deviation increase = 0.77, 95% confidence interval, 0.67-0.89). Associations with CRC risk were also found for six previously reported metabolic biomarkers of prevalent and/or incident CRC: sebacic acid (inverse association) and L-tryptophan, 3-hydroxybutyric acid, 9,12,13-TriHOME, valine, and 13-OxoODE (positive associations). Conclusions: These findings suggest that although the circulating metabolome may provide new etiological insights into the underlying causes of CRC development, its potential application for the identification of individuals at higher risk of developing CRC is limited. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Cancer & Metabolism 11 1 |
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Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
Untargeted metabolomics Colorectal cancer Early detection Cancer and Oncology Cancer och onkologi |
spellingShingle |
Untargeted metabolomics Colorectal cancer Early detection Cancer and Oncology Cancer och onkologi Vidman, Linda Zheng, Rui Bodén, Stina Ribbenstedt, Anton Gunter, Marc J. Palmqvist, Richard Harlid, Sophia Brunius, Carl van Guelpen, Bethany Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
topic_facet |
Untargeted metabolomics Colorectal cancer Early detection Cancer and Oncology Cancer och onkologi |
description |
Background: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, but if discovered at an early stage, the survival rate is high. The aim of this study was to identify novel markers predictive of future CRC risk using untargeted metabolomics. Methods: This study included prospectively collected plasma samples from 902 CRC cases and 902 matched cancer-free control participants from the population-based Northern Sweden Health and Disease Study (NSHDS), which were obtained up to 26 years prior to CRC diagnosis. Using reverse-phase liquid chromatography-mass spectrometry (LC-MS), data comprising 5015 metabolic features were obtained. Conditional logistic regression was applied to identify potentially important metabolic features associated with CRC risk. In addition, we investigated if previously reported metabolite biomarkers of CRC risk could be validated in this study population. Results: In the univariable analysis, seven metabolic features were associated with CRC risk (using a false discovery rate cutoff of 0.25). Two of these could be annotated, one as pyroglutamic acid (odds ratio per one standard deviation increase = 0.79, 95% confidence interval, 0.70-0.89) and another as hydroxytigecycline (odds ratio per one standard deviation increase = 0.77, 95% confidence interval, 0.67-0.89). Associations with CRC risk were also found for six previously reported metabolic biomarkers of prevalent and/or incident CRC: sebacic acid (inverse association) and L-tryptophan, 3-hydroxybutyric acid, 9,12,13-TriHOME, valine, and 13-OxoODE (positive associations). Conclusions: These findings suggest that although the circulating metabolome may provide new etiological insights into the underlying causes of CRC development, its potential application for the identification of individuals at higher risk of developing CRC is limited. |
format |
Article in Journal/Newspaper |
author |
Vidman, Linda Zheng, Rui Bodén, Stina Ribbenstedt, Anton Gunter, Marc J. Palmqvist, Richard Harlid, Sophia Brunius, Carl van Guelpen, Bethany |
author_facet |
Vidman, Linda Zheng, Rui Bodén, Stina Ribbenstedt, Anton Gunter, Marc J. Palmqvist, Richard Harlid, Sophia Brunius, Carl van Guelpen, Bethany |
author_sort |
Vidman, Linda |
title |
Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
title_short |
Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
title_full |
Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
title_fullStr |
Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
title_full_unstemmed |
Untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
title_sort |
untargeted plasma metabolomics and risk of colorectal cancer : an analysis nested within a large-scale prospective cohort |
publisher |
Umeå universitet, Institutionen för matematik och matematisk statistik |
publishDate |
2023 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218144 https://doi.org/10.1186/s40170-023-00319-x |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Cancer & Metabolism, 2023, 11:1, orcid:0000-0002-8958-975x orcid:0000-0002-9933-2843 orcid:0000-0001-8540-6891 orcid:0000-0002-9692-101X http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218144 doi:10.1186/s40170-023-00319-x PMID 37849011 ISI:001088049400001 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/s40170-023-00319-x |
container_title |
Cancer & Metabolism |
container_volume |
11 |
container_issue |
1 |
_version_ |
1789970625811447808 |