Pre-diagnostic anti-EBV antibodies and primary liver cancer risk: a population-based nested case-control study in southern China

• Published in: BMC cancer Vol. 23; no. 1; pp. 250 - 9
• Main Authors: Du, Yun, Yu, Xia, Chang, Ellen T., Lian, Shifeng, Wu, Biaohua, Li, Fugui, Chu, Bing, Wei, Kuangrong, Zhan, Jiyun, Liang, Xuejun, Ye, Weimin, Ji, Mingfang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.03.2023; BioMed Central; BMC
• Subjects: Antibodies; Antibodies, Viral; Antibody; Antigens; Antigens, Viral; Biomarkers; Capsid Proteins; Case-Control Studies; China - epidemiology; Epidemiology; Epstein-Barr virus; Epstein-Barr Virus Infections; Health aspects; Hepatitis B; Hepatitis B surface antigen; Hepatitis B Surface Antigens; Herpesvirus 4, Human; Humans; Identification and classification; Immunoglobulin A; Infections; Liver cancer; Liver Neoplasms - complications; Liver Neoplasms - diagnosis; Liver Neoplasms - epidemiology; Lymphoma; Males; Measurement; Medical diagnosis; Medical screening; Nasopharyngeal Neoplasms - diagnosis; Nested case-control study; Optical density; Population studies; Population-based; Population-based studies; Primary liver cancer; Risk factors; Sensitivity analysis; Serology; China; Population-based; Epstein-Barr virus; Primary liver cancer; Nested case-control study; Antibody; Epidemiology
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10709-5

We aimed to investigate associations between pre-diagnostic anti-Epstein-Barr virus (EBV) antibodies, including interactions with hepatitis B virus (HBV), and risk of primary liver cancer in southern China. In a population-based nested case-control study, we measured pre-diagnostic immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) in 125 primary liver cancer cases and 2077 matched controls. We also explored the interaction between HBV surface antigen (HBsAg) and anti-EBV antibodies. Participants with positive EBNA1-IgA, positive VCA-IgA or single-positive anti-EBV antibodies had two-fold odds of developing liver cancer, compared with seronegative subjects. The odds ratios (ORs) between the relative optical density of EBNA1-IgA and VCA-IgA and primary cancer, controlling for age and HBsAg, were 1.59 (95% confidence interval (CI): 1.17, 2.14) and 1.60 (95% CI: 1.07, 2.41), respectively. Subjects with both HBsAg and anti-EBV antibody seropositivity were at 50-fold increased risk compared with those negative for both biomarkers (OR: 50.67, 95% CI: 18.28, 140.46), yielding a relative excess risk due to interaction of 30.81 (95% CI: 3.42, 114.93). Pre-diagnostic seropositivity for EBNA1-IgA and/or VCA-IgA was positively associated with primary liver cancer risk, especially in combination with HBsAg positivity. EBV may interact with HBV in the development of primary liver cancer, and anti-EBV antibodies might be potential biomarkers for primary liver cancer in this high-risk population.