Metabolomic signatures of inflammation and metabolic dysregulation in relation to colorectal cancer risk
© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com..
BACKGROUND: Inflammation and metabolic dysregulation are associated with increased risk of colorectal cancer (CRC); the underlying mechanisms are not fully understood. We characterized metabolomic signatures of inflammation and metabolic dysregulation and evaluated the association of the signatures and individual metabolites with CRC risk.
METHODS: Among 684 incident CRC cases and 684 age-matched controls in the Nurses' Health Study (n = 818 women) and Health Professionals Follow-up Study (n = 550 men), we applied reduced rank and elastic net regression to 277 metabolites for markers of inflammation (CRP, IL6, TNFRSF1B, and GDF15) or metabolic dysregulation (body mass index, waist circumference, C-peptide, and adiponectin) to derive metabolomic signatures. We evaluated the association of the signatures and individual metabolites with CRC using multivariable conditional logistic regression. All statistical tests were 2-sided.
RESULTS: We derived a signature of 100 metabolites that explained 24% of variation in markers of inflammation and a signature of 73 metabolites that explained 27% of variation in markers of metabolic dysregulation. Among men, both signatures were associated with CRC (odds ratio per 1-standard deviation increase, inflammation = 1.34, 95% confidence interval 1.07 to 1.68; metabolic dysregulation = 1.25, 1.00 to 1.55); neither signature was associated with CRC in women. Eleven metabolites were individually associated with CRC and biomarkers of inflammation or metabolic dysregulation among either men or women.
CONCLUSION: We derived metabolomic signatures and identified individual metabolites associated with inflammation, metabolic dysregulation, and CRC, highlighting several metabolites as promising candidates involved in the inflammatory and metabolic dysregulation pathways for CRC incidence.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of the National Cancer Institute - (2024) vom: 01. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bever, Alaina M [VerfasserIn] |
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Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/jnci/djae047 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Inflammation and metabolic dysregulation are associated with increased risk of colorectal cancer (CRC); the underlying mechanisms are not fully understood. We characterized metabolomic signatures of inflammation and metabolic dysregulation and evaluated the association of the signatures and individual metabolites with CRC risk | ||
| 520 | |a METHODS: Among 684 incident CRC cases and 684 age-matched controls in the Nurses' Health Study (n = 818 women) and Health Professionals Follow-up Study (n = 550 men), we applied reduced rank and elastic net regression to 277 metabolites for markers of inflammation (CRP, IL6, TNFRSF1B, and GDF15) or metabolic dysregulation (body mass index, waist circumference, C-peptide, and adiponectin) to derive metabolomic signatures. We evaluated the association of the signatures and individual metabolites with CRC using multivariable conditional logistic regression. All statistical tests were 2-sided | ||
| 520 | |a RESULTS: We derived a signature of 100 metabolites that explained 24% of variation in markers of inflammation and a signature of 73 metabolites that explained 27% of variation in markers of metabolic dysregulation. Among men, both signatures were associated with CRC (odds ratio per 1-standard deviation increase, inflammation = 1.34, 95% confidence interval 1.07 to 1.68; metabolic dysregulation = 1.25, 1.00 to 1.55); neither signature was associated with CRC in women. Eleven metabolites were individually associated with CRC and biomarkers of inflammation or metabolic dysregulation among either men or women | ||
| 520 | |a CONCLUSION: We derived metabolomic signatures and identified individual metabolites associated with inflammation, metabolic dysregulation, and CRC, highlighting several metabolites as promising candidates involved in the inflammatory and metabolic dysregulation pathways for CRC incidence | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Hang, Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Dong Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Tabung, Fred K |e verfasserin |4 aut | |
| 700 | 1 | |a Ugai, Tomotaka |e verfasserin |4 aut | |
| 700 | 1 | |a Ogino, Shuji |e verfasserin |4 aut | |
| 700 | 1 | |a Meyerhardt, Jeffrey A |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Andrew T |e verfasserin |4 aut | |
| 700 | 1 | |a Eliassen, A Heather |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Liming |e verfasserin |4 aut | |
| 700 | 1 | |a Stampfer, Meir J |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Mingyang |e verfasserin |4 aut | |
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