Untargeted plasma metabolomics and risk of colorectal cancer—an analysis nested within a large-scale prospective cohort
Abstract 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 includ...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Cancer & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40170-023-00319-x |
| _version_ | 1797556962070626304 |
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| author | Linda Vidman Rui Zheng Stina Bodén Anton Ribbenstedt Marc J. Gunter Richard Palmqvist Sophia Harlid Carl Brunius Bethany Van Guelpen |
| author_facet | Linda Vidman Rui Zheng Stina Bodén Anton Ribbenstedt Marc J. Gunter Richard Palmqvist Sophia Harlid Carl Brunius Bethany Van Guelpen |
| author_sort | Linda Vidman |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:10:37Z |
| format | Article |
| id | doaj.art-ea427728981044229ce5bd73a5991b65 |
| institution | Directory Open Access Journal |
| issn | 2049-3002 |
| language | English |
| last_indexed | 2024-03-10T17:10:37Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer & Metabolism |
| spelling | doaj.art-ea427728981044229ce5bd73a5991b652023-11-20T10:41:05ZengBMCCancer & Metabolism2049-30022023-10-0111111310.1186/s40170-023-00319-xUntargeted plasma metabolomics and risk of colorectal cancer—an analysis nested within a large-scale prospective cohortLinda Vidman0Rui Zheng1Stina Bodén2Anton Ribbenstedt3Marc J. Gunter4Richard Palmqvist5Sophia Harlid6Carl Brunius7Bethany Van Guelpen8Department of Radiation Sciences, Oncology, Umeå UniversityDepartment of Surgical Sciences, Medical Epidemiology, Uppsala UniversityDepartment of Radiation Sciences, Oncology, Umeå UniversityDepartment of Biology and Biological Engineering, Chalmers University of TechnologyNutrition and Metabolism Branch, International Agency for Research on CancerDepartment of Medical Biosciences, Pathology, Umeå UniversityDepartment of Radiation Sciences, Oncology, Umeå UniversityDepartment of Biology and Biological Engineering, Chalmers University of TechnologyDepartment of Radiation Sciences, Oncology, Umeå UniversityAbstract 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.https://doi.org/10.1186/s40170-023-00319-xUntargeted metabolomicsColorectal cancerEarly detection |
| spellingShingle | Linda Vidman Rui Zheng Stina Bodén Anton Ribbenstedt Marc J. Gunter Richard Palmqvist Sophia Harlid Carl Brunius Bethany Van Guelpen Untargeted plasma metabolomics and risk of colorectal cancer—an analysis nested within a large-scale prospective cohort Cancer & Metabolism Untargeted metabolomics Colorectal cancer Early detection |
| title | 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_short | 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 |
| topic | Untargeted metabolomics Colorectal cancer Early detection |
| url | https://doi.org/10.1186/s40170-023-00319-x |
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