Circulating proteins and risk of pancreatic cancer: a case-subcohort study among Chinese adults. (22nd January 2022)

• Record Type: Journal Article
• Authors: Kartsonaki, Christiana; Pang, Yuanjie; Millwood, Iona; Yang, Ling; Guo, Yu; Walters, Robin; Lv, Jun; Hill, Michael; Yu, Canqing; Chen, Yiping; Chen, Xiaofang; O'Neill, Eric; Chen, Junshi; Travis, Ruth C; Clarke, Robert; Li, Liming; Chen, Zhengming; Holmes, Michael V
• Is Part Of: International journal of epidemiology. Volume 51:Number 3(2022)
• Page Start: 817
• Page End: 829
• Publication Date: 2022-01-22
• Subjects: Pancreatic cancer -- proteomics -- biomarkers -- risk prediction -- early diagnosis; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyab274
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: 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.