HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma

被引：11

作者：

Liu, Zhiwei ^{[1
]}

Huang, Chih-Jen ^{[2
]}

Huang, Yu-Han ^{[3
]}

Pan, Mei-Hung ^{[2
]}

Lee, Mei-Hsuan ^{[3
]}

Yu, Kelly J. ^{[1
]}

Pfeiffer, Ruth M. ^{[1
]}

Viard, Mathias ^{[4
]}

Yuki, Yuko ^{[4
]}

Gao, Xiaojiang ^{[5
]}

Carrington, Mary ^{[4
,6
]}

Chen, Chien-Jen ^{[2
]}

Hildesheim, Allan ^{[1
]}

Yang, Hwai-, I ^{[2
,3
,7
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[2] Acad Sinica, Genom Res Ctr, 128 Acad Rd Sect 2, Taipei 11529, Taiwan

[3] Natl Yang Ming Univ, Inst Clin Med, Taipei, Taiwan

[4] Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA

[5] NCI, Lab Integrat Canc Immunol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[6] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA

[7] Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung, Taiwan

来源：

JOURNAL OF INFECTIOUS DISEASES | 2021年 / 224卷 / 10期

基金：

美国国家卫生研究院;

关键词：

hepatocellular carcinoma; hepatitis B virus; human leukocyte antigen; cirrhosis; Taiwan; zygosity; HETEROZYGOTE ADVANTAGE; ALLELES;

D O I：

10.1093/infdis/jiab207

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Diversity in the 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 (MCC). Methods. 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 2 HLA alleles at that locus. Results. Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (P-trend = 1.18 x 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 (P-trend = .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. Conclusions. Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.

引用

页码：1796 / 1805

页数：10

共 23 条

[1] HLA Heterozygote Advantage against HIV-1 Is Driven by Quantitative and Qualitative Differences in HLA Allele-Specific Peptide Presentation [J].