Jill Koshiol1, Yu-Tang Gao2, Amanda Corbel3, Troy J Kemp4, Ming-Chang Shen5, Allan Hildesheim3, Ann W Hsing6, Asif Rashid7, Bingsheng Wang8, Ruth M Pfeiffer9, Ligia A Pinto4. 1. Infections Immunoepidemiology Branch, Division of Cancer Epidemiology Genetics, National Cancer Institute, MD, USA. Electronic address: koshiolj@mail.nih.gov. 2. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China. 3. Infections Immunoepidemiology Branch, Division of Cancer Epidemiology Genetics, National Cancer Institute, MD, USA. 4. HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos, Biomedical Research, Inc, Frederick, MD, USA. 5. Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, China. 6. Stanford Cancer Institute, Stanford School of Medicine, Palo Alto, CA, USA; Stanford Prevention Research Center, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA. 7. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Department of General Surgery, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China. 9. Biostastitics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, MD, USA.
Abstract
BACKGROUND: Inflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy. METHODS: We analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1-2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification. RESULTS: 26 proteins (53%) had P values for the trend across categories ≤0.001, with associations for a one category increase ranging from 1.52 (95% CI: 1.20-1.94) for CC motif ligand 4 to 4.00 (95% CI: 2.76-5.79) for interleukin (IL)-8. Soluble tumor necrosis factor receptor 2 (sTNFR2), IL-6, sTNFR1, CC motif ligand 20 (CCL20), vascular cell adhesion molecule 1, IL-16, and granulocyte colony-stimulating factor had P values ≤0.001 for early GBC. Of those, IL-6, IL-16, CCL20, and STNFR1 were included in the inflammation score. In a high-risk setting with a pre-test disease risk of 10% (e.g., elderly patients) and using an inflammation score cutoff that provides 90% sensitivity, 39% of patients on the waiting list would be predicted to be positive, and 23% of those would be predicted to have GBC. CONCLUSION: These results highlight the strong associations of inflammatory proteins with GBC risk and their potential clinical utility. Larger studies are needed to identify the most effective combinations of inflammatory proteins for detecting early GBC and precursor lesions. Published by Elsevier Ltd.
BACKGROUND: Inflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy. METHODS: We analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1-2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification. RESULTS: 26 proteins (53%) had P values for the trend across categories ≤0.001, with associations for a one category increase ranging from 1.52 (95% CI: 1.20-1.94) for CC motif ligand 4 to 4.00 (95% CI: 2.76-5.79) for interleukin (IL)-8. Soluble tumor necrosis factor receptor 2 (sTNFR2), IL-6, sTNFR1, CC motif ligand 20 (CCL20), vascular cell adhesion molecule 1, IL-16, and granulocyte colony-stimulating factor had P values ≤0.001 for early GBC. Of those, IL-6, IL-16, CCL20, and STNFR1 were included in the inflammation score. In a high-risk setting with a pre-test disease risk of 10% (e.g., elderly patients) and using an inflammation score cutoff that provides 90% sensitivity, 39% of patients on the waiting list would be predicted to be positive, and 23% of those would be predicted to have GBC. CONCLUSION: These results highlight the strong associations of inflammatory proteins with GBC risk and their potential clinical utility. Larger studies are needed to identify the most effective combinations of inflammatory proteins for detecting early GBC and precursor lesions. Published by Elsevier Ltd.
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