| Title: | Pre-diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population-based cohort studies from the United States and the United Kingdom |
| Journal: | International Journal of Cancer |
| Published: | 11 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38861327/ |
| DOI: | https://doi.org/10.1002/ijc.35054 |
Publication 11872
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Abstract
Previous studies suggest a role for inflammation in hepatocarcinogenesis. However, no study has comprehensively evaluated associations between circulating inflammatory proteins and risk of hepatocellular carcinoma (HCC) among the general population. We conducted a nested case-control study in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) with 56 pairs of incident HCC cases and controls. External validation was performed in the UK Biobank (34 HCC cases and 48,471 non-HCC controls). Inflammatory protein levels were measured in pre-diagnostic plasma using the Olink® Inflammation Panel. We used conditional logistic regression to calculate multivariable odds ratios (ORs) with 95% confidence intervals (CIs) for associations between a 1-standard deviation (SD) increase in biomarker levels and HCC risk, considering a statistically significant threshold of false discovery rate (FDR)-adjusted p < .05. In the NHS/HPFS, among 70 analyzed proteins with call rates >80%, 15 proteins had significant associations with HCC risk (pFDR < .05). Two proteins (stem cell factor, OR per SD = 0.31, 95% CI = 0.16-0.58; tumor necrosis factor superfamily member 12, OR per SD = 0.51, 95% CI = 0.31-0.85) were inversely associated whereas 13 proteins were positively associated with risk of HCC; positive ORs per SD ranged from 1.73 for interleukin (IL)-10 to 2.35 for C-C motif chemokine-19. A total of 11 proteins were further replicated in the UK Biobank. Seven of the eight selected positively associated proteins also showed positive associations with HCC risk by enzyme-linked immunosorbent assay, with ORs ranging from 1.56 for IL-10 to 2.72 for hepatocyte growth factor. More studies are warranted to further investigate the roles of these observed inflammatory proteins in HCC etiology, early detection, risk stratification, and disease treatment.</p>
11 Authors
- Longgang Zhao
- Xinyuan Zhang
- Brenda M. Birmann
- Christopher J. Danford
- Michelle Lai
- Tracey G. Simon
- Andrew T. Chan
- Edward L. Giovannucci
- Long Ngo
- Towia A. Libermann
- Xuehong Zhang
1 Application
| Application ID | Title |
|---|---|
| 87303 | Improving liver health in humans: Elucidating the role of genetics, biomarkers, and environment in liver biology, etiology, progression, and prognosis |
Enabling scientific discoveries that improve human health