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HLA zygosity increases risk of hepatitis B virus-associated hepatocellular carcinoma

  1. Author:
    Liu, Zhiwei
    Huang, Chih-Jen
    Huang, Yu-Han
    Pan, Mei-Hung
    Lee, Mei-Hsuan
    Yu, Kelly J
    Pfeiffer, Ruth M
    Viard, Mathias
    Yuki, Yuko
    Gao, Xiaojiang
    Carrington, Mary
    Chen, Chien-Jen
    Hildesheim, Allan
    Yang, Hwai-I

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Genomics Research Center, Academia Sinica, Taipei, Taiwan., Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,
    1. Year: 2021
    2. Date: Apr 14
  2. Journal: The Journal of Infectious Diseases
  4. Type of Article: Article
  1. Abstract:

    Diversity in the human leukocyte antigen (HLA) genes might be associated with disease outcomes - the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). We utilized DNA from >10,000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the two HLA alleles at that locus. Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend=1.18×10 -7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend=0.031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio=1.40, 95% confidence interval=1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control. Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC. Published by Oxford University Press for the Infectious Diseases Society of America 2021.

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External Sources

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  2. DOI: 10.1093/infdis/jiab207
  3. PMID: 33852009
  4. PII : 6225842

Library Notes

  1. Fiscal Year: FY2020-2021
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