Skip to main content
Top
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Hepatitis B | Research

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

Authors: Yun Du, Xia Yu, Ellen T. Chang, Shifeng Lian, Biaohua Wu, Fugui Li, Bing Chu, Kuangrong Wei, Jiyun Zhan, Xuejun Liang, Weimin Ye, Mingfang Ji

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Khan G, Fitzmaurice C, Naghavi M, Ahmed LA. Global and regional incidence, mortality and disability-adjusted life-years for Epstein-Barr virus-attributable malignancies, 1990–2017. BMJ Open. 2020;10:e037505.CrossRefPubMedPubMedCentral Khan G, Fitzmaurice C, Naghavi M, Ahmed LA. Global and regional incidence, mortality and disability-adjusted life-years for Epstein-Barr virus-attributable malignancies, 1990–2017. BMJ Open. 2020;10:e037505.CrossRefPubMedPubMedCentral
2.
go back to reference Young LS, Yap LF, Murray PG. Epstein–Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016;16(12):789–802.CrossRefPubMed Young LS, Yap LF, Murray PG. Epstein–Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016;16(12):789–802.CrossRefPubMed
3.
5.
go back to reference Bray F, Colombet M, Mery L, Piñeros M, Znaor A, Zanetti R, et al. Cancer incidence in five continents, Vol. XI. IARC scientific publication no. 166. Lyon: International Agency for Research on Cancer; 2021. https://publications.iarc.fr/597. Accessed 21 Oct 2021. Bray F, Colombet M, Mery L, Piñeros M, Znaor A, Zanetti R, et al. Cancer incidence in five continents, Vol. XI. IARC scientific publication no. 166. Lyon: International Agency for Research on Cancer; 2021. https://​publications.​iarc.​fr/​597. Accessed 21 Oct 2021.
6.
7.
go back to reference Tanaka M, Katayama F, Kato H, Tanaka H, Wang J, Qiao YL, et al. Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol. 2011;21:401–16.CrossRefPubMedPubMedCentral Tanaka M, Katayama F, Kato H, Tanaka H, Wang J, Qiao YL, et al. Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. J Epidemiol. 2011;21:401–16.CrossRefPubMedPubMedCentral
8.
go back to reference Yang F, Ma L, Yang Y, Liu W, Zhao J, Chen X, et al. Contribution of hepatitis B virus infection to the aggressiveness of primary liver cancer: A clinical epidemiological study in eastern China. Front Oncol. 2019;9:370.CrossRefPubMedPubMedCentral Yang F, Ma L, Yang Y, Liu W, Zhao J, Chen X, et al. Contribution of hepatitis B virus infection to the aggressiveness of primary liver cancer: A clinical epidemiological study in eastern China. Front Oncol. 2019;9:370.CrossRefPubMedPubMedCentral
9.
go back to reference Ji M, Liu Z, Chang ET, Yu X, Wu B, Deng L, et al. Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China. Sci Rep. 2018;8:12787. Ji M, Liu Z, Chang ET, Yu X, Wu B, Deng L, et al. Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China. Sci Rep. 2018;8:12787.
10.
go back to reference Sugawara Y, Makuuchi M, Kato N, Shimotohno K, Takada K. Enhancement of hepatitis C virus replication by Epstein-Barr virus-encoded nuclear antigen 1. EMBO J. 1999;18:5755.CrossRefPubMedPubMedCentral Sugawara Y, Makuuchi M, Kato N, Shimotohno K, Takada K. Enhancement of hepatitis C virus replication by Epstein-Barr virus-encoded nuclear antigen 1. EMBO J. 1999;18:5755.CrossRefPubMedPubMedCentral
11.
go back to reference Sugawara Y, Makuuchi M, Takada K. Detection of Epstein-Barr virus DNA in hepatocellular carcinoma tissues from hepatitis C-positive patients. Scand J Gastroenterol. 2000;35:981–4.CrossRefPubMed Sugawara Y, Makuuchi M, Takada K. Detection of Epstein-Barr virus DNA in hepatocellular carcinoma tissues from hepatitis C-positive patients. Scand J Gastroenterol. 2000;35:981–4.CrossRefPubMed
12.
go back to reference Junying J, Herrmann K, Davies G, Lissauer D, Bell A, Timms J, et al. Absence of epstein–barr virus DNA in the tumor cells of european hepatocellular carcinoma. Virology. 2003;306:236–43.CrossRefPubMed Junying J, Herrmann K, Davies G, Lissauer D, Bell A, Timms J, et al. Absence of epstein–barr virus DNA in the tumor cells of european hepatocellular carcinoma. Virology. 2003;306:236–43.CrossRefPubMed
13.
go back to reference zur Hausen A, van Beek J, Bloemena E, ten Kate FJ, Meijer CJLM, van den Brule AJC. No role for Epstein-Barr virus in Dutch hepatocellular carcinoma: a study at the DNA, RNA and protein levels. J Gen Virol. 2003;84(Pt 7):1863–9.PubMed zur Hausen A, van Beek J, Bloemena E, ten Kate FJ, Meijer CJLM, van den Brule AJC. No role for Epstein-Barr virus in Dutch hepatocellular carcinoma: a study at the DNA, RNA and protein levels. J Gen Virol. 2003;84(Pt 7):1863–9.PubMed
14.
go back to reference Liu Z, Ji MF, Huang QH, Fang F, Liu Q, Jia WH, et al. Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in southern China. Am J Epidemiol. 2013;177:242–50.CrossRefPubMed Liu Z, Ji MF, Huang QH, Fang F, Liu Q, Jia WH, et al. Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in southern China. Am J Epidemiol. 2013;177:242–50.CrossRefPubMed
15.
go back to reference Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28:112–25.CrossRefPubMed Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28:112–25.CrossRefPubMed
16.
17.
go back to reference Zou GY. On the estimation of additive interaction by use of the four-by-two table and beyond. Am J Epidemiol. 2008;168:212–24.CrossRefPubMed Zou GY. On the estimation of additive interaction by use of the four-by-two table and beyond. Am J Epidemiol. 2008;168:212–24.CrossRefPubMed
19.
go back to reference Stevens SJC, Verkuijlen SAWM, Hariwiyanto B, Harijadi FJ, Paramita DK, et al. Diagnostic value of measuring Epstein-Barr virus (EBV) DNA load and carcinoma-specific viral mRNA in relation to anti-EBV immunoglobulin A (IgA) and IgG antibody levels in blood of nasopharyngeal carcinoma patients from Indonesia. J Clin Microbiol. 2005:43(7):3066–73. Stevens SJC, Verkuijlen SAWM, Hariwiyanto B, Harijadi FJ, Paramita DK, et al. Diagnostic value of measuring Epstein-Barr virus (EBV) DNA load and carcinoma-specific viral mRNA in relation to anti-EBV immunoglobulin A (IgA) and IgG antibody levels in blood of nasopharyngeal carcinoma patients from Indonesia. J Clin Microbiol. 2005:43(7):3066–73.
20.
go back to reference de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8:e180–90.CrossRefPubMed de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8:e180–90.CrossRefPubMed
22.
23.
go back to reference Akhter S, Liu H, Prabhu R, DeLucca C, Bastian F, Garry RF, et al. Epstein-Barr virus and human hepatocellular carcinoma. Cancer Lett. 2003;192:49–57.CrossRefPubMed Akhter S, Liu H, Prabhu R, DeLucca C, Bastian F, Garry RF, et al. Epstein-Barr virus and human hepatocellular carcinoma. Cancer Lett. 2003;192:49–57.CrossRefPubMed
24.
go back to reference Knol MJ, Vandenbroucke JP, Scott P, Egger M. What do case-control studies estimate? Survey of methods and assumptions in published case-control research. Am J Epidemiol. 2008;168:1073–81.CrossRefPubMed Knol MJ, Vandenbroucke JP, Scott P, Egger M. What do case-control studies estimate? Survey of methods and assumptions in published case-control research. Am J Epidemiol. 2008;168:1073–81.CrossRefPubMed
25.
go back to reference Bas BB, Groenwold RHH. Identification of causal effects in case-control studies. BMC Med Res Methodol. 2022;22:7. Bas BB, Groenwold RHH. Identification of causal effects in case-control studies. BMC Med Res Methodol. 2022;22:7.
Metadata
Title
Pre-diagnostic anti-EBV antibodies and primary liver cancer risk: a population-based nested case-control study in southern China
Authors
Yun Du
Xia Yu
Ellen T. Chang
Shifeng Lian
Biaohua Wu
Fugui Li
Bing Chu
Kuangrong Wei
Jiyun Zhan
Xuejun Liang
Weimin Ye
Mingfang Ji
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10709-5

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine