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Abstract Details
Immunologic markers and risk of hepatocellular carcinoma in hepatitis B virus- and hepatitis C virus-infected individuals
Jill Koshiol1, Ilona Argirion1, Zhiwei Liu1, Tram Kim Lam2, Thomas R O'Brien1, Kelly Yu1, Katherine A McGlynn1, Jessica L Petrick13, Ligia Pinto4, Chien-Jen Chen56, Allan Hildesheim1, Ruth M Pfeiffer1, Mei-Hsuan Lee7, Hwai-I Yang5
Author information
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
2Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA.
3School of Medicine, Slone Epidemiology Center, Boston University, Boston, MA, USA.
4HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Leidos, Biomedical Research, Inc, Frederick, MD, USA.
5Genomics Research Center, Academia Sinica, Taipei, Taiwan.
6Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
7National Yang Ming Chiao Tung University, Taipei, Taiwan.
Abstract
Background: Clinical and experimental studies suggest immunologic proteins contribute to hepatocellular carcinoma (HCC) development.
Aim: To evaluate circulating immunologic markers and HCC risk.
Methods: From a Taiwanese cohort of chronically hepatitis B virus (HBV)-infected individuals followed over time (REVEAL-HBV), we sampled 175 who developed HCC, 117 cirrhosis only, and 165 non-cirrhotic controls. From a similar Taiwanese cohort of chronically hepatitis C virus (HCV)-infected individuals (REVEAL-HCV), we included 94 individuals who developed HCC, 68 cirrhosis only and 100 non-cirrhotic controls. We compared pre-diagnostic plasma levels of 102 markers in HCC cases to non-cirrhotic and cirrhotic controls using polytomous logistic regression. A priori markers included insulin-like growth factor binding protein-3 (IGFBP-3), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6). P-values for other markers were corrected for multiple testing (false discovery rate = 10%).
Results: In both REVEAL-HBV and REVEAL-HCV, increasing levels of ICAM-1 were associated with increased risk of HCC compared to non-cirrhotic controls (P-trend 0.02 and 0.001, respectively). In both REVEAL-HBV and REVEAL-HCV, two novel markers [C-X-C motif chemokine 11 (CXCL11) and hepatocyte growth factor (HGF)] were positively associated [strongest odds ratioquartile 4 versus 1(OR) 4.55 for HGF in HCV], while two [complement factor H related 5 (CFHR5) and stem cell factor (SCF)] were negatively associated (strongest ORQ4vQ1 0.14 for SCF in HCV) with development of HCC compared to non-cirrhotic controls.
Conclusions: We confirmed the association for ICAM-1 and identified 4 additional proteins associated with HBV- and HCV-related HCC. These findings highlight the importance of immunologic processes in HBV- and HCV-related HCC.