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Metabolomic signatures of inflammation and metabolic dysregulation in relation to colorectal cancer risk.
- Source :
-
Journal of the National Cancer Institute [J Natl Cancer Inst] 2024 Jul 01; Vol. 116 (7), pp. 1126-1136. - Publication Year :
- 2024
-
Abstract
- 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.<br />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 (C-reactive protein, interleukin 6, tumor necrosis factor receptor superfamily member 1B, and growth differentiation factor 15) 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.<br />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 [OR] = 1.34, 95% confidence interval [CI] = 1.07 to 1.68 per 1-standard deviation increase, inflammation; OR = 1.25, 95% CI = 1.00 to 1.55 metabolic dysregulation); neither signature was associated with CRC in women. A total of 11 metabolites were individually associated with CRC and biomarkers of inflammation or metabolic dysregulation among either men or women.<br />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.<br /> (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Humans
Male
Female
Middle Aged
Case-Control Studies
Aged
Risk Factors
Adult
Interleukin-6 metabolism
Interleukin-6 blood
Adiponectin metabolism
Adiponectin blood
Waist Circumference
C-Peptide blood
C-Peptide metabolism
Metabolome
Follow-Up Studies
Biomarkers, Tumor metabolism
Prospective Studies
Logistic Models
Colorectal Neoplasms epidemiology
Colorectal Neoplasms metabolism
Inflammation metabolism
Metabolomics
Body Mass Index
C-Reactive Protein analysis
C-Reactive Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2105
- Volume :
- 116
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of the National Cancer Institute
- Publication Type :
- Academic Journal
- Accession number :
- 38430005
- Full Text :
- https://doi.org/10.1093/jnci/djae047