Journal article
Circulating proteins and risk of pancreatic cancer: a case-subcohort study among Chinese adults
- Abstract:
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Background
Pancreatic cancer has a very poor prognosis. Biomarkers that may help predict or diagnose pancreatic cancer may lead to earlier diagnosis and improved survival.
Methods
The prospective China Kadoorie Biobank (CKB) recruited 512 891 adults aged 30–79 years during 2004–08, recording 702 incident cases of pancreatic cancer during 9 years of follow-up. We conducted a case-subcohort study measuring 92 proteins in 610 cases and a subcohort of 623 individuals, using the OLINK immuno-oncology panel in stored baseline plasma samples. Cox regression with the Prentice pseudo-partial likelihood was used to estimate adjusted hazard ratios (HRs) for risk of pancreatic cancer by protein levels.
Results
Among 1233 individuals (including 610 cases), several chemokines, interleukins, growth factors and membrane proteins were associated with risk of pancreatic cancer, with adjusted HRs per 1 standard deviation (SD) of 0.86 to 1.86, including monocyte chemotactic protein 3 (MCP3/CCL7) {1.29 [95% CI (confidence interval) (1.10, 1.51)]}, angiopoietin-2 (ANGPT2) [1.27 (1.10, 1.48)], interleukin-18 (IL18) [1.24 (1.07, 1.43)] and interleukin-6 (IL6) [1.21 (1.06, 1.38)]. Associations between some proteins [e.g. matrix metalloproteinase-7 (MMP7), hepatocyte growth factor (HGF) and tumour necrosis factor receptor superfamily member 9 [TNFRSF9)] and risk of pancreatic cancer were time-varying, with higher levels associated with higher short-term risk. Within the first year, the discriminatory ability of a model with known risk factors (age, age squared, sex, region, smoking, alcohol, education, diabetes and family history of cancer) was increased when several proteins were incorporated (weighted C-statistic changed from 0.85 to 0.99; P for difference = 4.5 × 10–5), although only a small increase in discrimination (0.77 to 0.79, P = 0.04) was achieved for long-term risk.
Conclusions
Several plasma proteins were associated with subsequent diagnosis of pancreatic cancer. The potential clinical utility of these biomarkers warrants further investigation.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 882.5KB, Terms of use)
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- Publisher copy:
- 10.1093/ije/dyab274
Authors
- Publisher:
- Oxford University Press
- Journal:
- International Journal of Epidemiology More from this journal
- Volume:
- 51
- Issue:
- 3
- Pages:
- 817–829
- Publication date:
- 2022-01-22
- Acceptance date:
- 2021-12-31
- DOI:
- EISSN:
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1464-3685
- ISSN:
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0300-5771
- Pmid:
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35064782
- Language:
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English
- Keywords:
- Pubs id:
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1235729
- Local pid:
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pubs:1235729
- Deposit date:
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2022-02-16
Terms of use
- Copyright holder:
- Kartsonaki et al.
- Copyright date:
- 2022
- Rights statement:
- ©2022 The Author(s). Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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