Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer

Liu, Zhiwei; Derkach, Andriy; Yu, Kelly J.; Yeager, Meredith; Chang, Yu Sun; Chen, Chien Jen; Gyllensten, Ulf; Lan, Qing; Lee, Hsuan-Shu; McKay, James; Rothman, Nathaniel; Yang, Hwai I.; Hildesheim, Allan; Pfeiffer, Ruth M.

doi:10.1158/0008-5472.can-20-2292

Cited by 18 publications

(23 citation statements)

References 23 publications

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“…157,176,177). A contributing role of class II HLA molecules (encoded by HLA-DR, HLA-DQ, HLA-DM, and HLA-DP), which present extracellular antigens to helper T cells that in turn stimulate antibody-producing B cells, is also suggested by studies in Chinese, Tunisian, and Caucasian populations (178), as well as findings from one GWAS (168,179), but not another GWAS (180), which found associations with the class I region but not the class II region.…”

Section: Genome-wide Association Studies and The Human Leukocyte Antigen Regionmentioning

confidence: 93%

The Evolving Epidemiology of Nasopharyngeal Carcinoma

Chang

Zeng

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

238

160

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Background: The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the oncogenic Epstein-Barr virus (EBV), the unique association with intake of Chinese-style salt-preserved fish, and etiologic heterogeneity by histologic subtype.Methods: This review summarizes the current epidemiologic literature on NPC, highlighting recent results from our populationbased case-control study in southern China.Results: Findings from our case-control study provide new insight into the epidemiology of NPC, including a diminished role of Chinese-style salt-preserved fish, a profound impact of EBV genetic sequence variation, modest positive associations with passive smoking and household air pollution, and possible effects of oral health and the oral microbiome. Recent findings from other studies include a protective association with infectious mononucleosis, suggesting a causal role of early EBV infection; familial risk conferred by shared genetic variation in the host antibody-mediated immune response to EBV infection; and an unclear association with occupational exposure to formaldehyde.Conclusions: To shed further light on the interplay of environmental, genetic, and viral causes of NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.Impact: New epidemiologic findings have reshaped the causal model for NPC.

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Section: Genome-wide Association Studies and The Human Leukocyte Antigen Regionmentioning

confidence: 93%

The Evolving Epidemiology of Nasopharyngeal Carcinoma

Chang

Zeng

et al. 2021

Cancer Epidemiology, Biomarkers &Amp; Prevention

238

160

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“…However, in the present study that evaluated cancers that are not caused by viral infection and that do not arise in immune cells, we observed little evidence for an increase in risk of non-virus-associated solid tumors or 12 types individually with HLA homozygosity. Of note, even for cancers that typically have a high mutational load (i.e., higher number of neoepitopes) or associated with individuals SNPs within the HLA region, such as lung cancer ( Efremova et al, 2017 ; Liu et al, 2021 ), no association with HLA homozygosity was noted.…”

Section: Discussionmentioning

confidence: 99%

“…The present study is composed of 29,343 subjects of European ancestry who participated in 10 studies across 12 cancer sites as primary diagnoses, including cancers of the bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis, which have been described in detail elsewhere ( Liu et al, 2021 ; Supplementary Material and Supplementary Table 1 ). Cases selected were either histopathologically confirmed or identified through linkage to the Cancer Registers as primary cancers.…”

Section: Methodsmentioning

confidence: 99%

“…Genome-wide association study platforms used include the Illumina Human1M-Duo BeadChip, Illumina Human Omni2.5-8 BeadChip, Illumina HumanHap 550K, Illumina HumanHap 610K, Illumina HumanHap 660W, Illumina HumanOmni1, and Illumina OmniExpress. Quality control was performed within each study and has been described in detail elsewhere ( Liu et al, 2021 ). Briefly, we excluded single-nucleotide polymorphisms (SNPs) with missing rate > 10% and subjects with missing SNPs > 10% ( N = 366) and subjects with missing information on sex and/or age at diagnosis ( N = 104).…”

Section: Methodsmentioning

confidence: 99%

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Association Between Human Leukocyte Antigen Class I and II Diversity and Non-virus-associated Solid Tumors

Liu

Hildesheim

2021

Front. Genet.

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Homozygosity at human leukocyte antigen (HLA) loci might lead to reduced immunosurveillance and increased disease risk, including cancers caused by infection or of hematopoietic origin. To investigate the association between HLA zygosity and risk of non-virus-associated solid tumors, we leveraged genome-wide association study (GWAS) data from over 28,000 individuals of European ancestry who participated in studies of 12 cancer sites (bladder, brain, breast, colon, endometrial, kidney, lung, ovary, pancreas, prostate, skin, and testis). Information on HLA zygosity was obtained by imputation; individuals were classified as homozygotes at a given locus when imputed to carry the same four-digit allele at that locus. We observed no evidence for an association between zygosity at six HLA loci and all cancers combined. Increase in number of homozygous at HLA class I loci, class II loci, or class I and II loci was also not associated with cancer overall (Ptrend = 0.28), with adjusted odds ratios (ORs) for risk-per-locus of 1.00 [95% confidence intervals (CIs) = 0.97, 1.03], 1.02 (0.99, 1.04), and 1.01 (0.99, 1.02), respectively. This study does not support a strong role for HLA zygosity on risk of non-virus-associated solid tumors.

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“… 15 HLA gene variation is associated with risk of cancers, particularly for those with infectious etiology. 18 For instance, variants of HLA-DPA1 and HLA-DPB1 have been associated with cervical cancer, a cancer that is caused by human papillomavirus (HPV) infection. 19 As another example, HLA-A*11:01 could be a protective marker for nasopharyngeal carcinoma caused by Epstein–Barr virus (EBV).…”

Section: Introductionmentioning

confidence: 99%

Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese

Mai

Chen

et al. 2021

JHC

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Introduction Genome-wide association studies identified susceptibility loci in the major histocompatibility complex region for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the causal variants underlying HBV-related HCC pathogenesis remain elusive. Methods With a total of 1,161 HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and evaluated the associations of these variants with the risk of HBV-related HCC. Conditional analyses were used to identify independent signals associated with the risk of HBV-related HCC (P false-discovery rate (FDR) <0.20). A total of 14,930 variants within the MHC region were genotyped or imputed. Results We identified two variants, rs114401688 (P = 1.05 × 10 −6 , P FDR = 2.43 × 10 −3 ) and rs115126566 (P = 9.04 × 10 −5 , P FDR = 1.77 × 10 −1 ), that are independently associated with the risk of HBV-related HCC. Single nucleotide polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously reported SNP rs9275319. In the current study, we found that its association with HCC could be explained by HLA-DQB1*04 and HLA-DRB1*04. SNP rs115126566 is a novel risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 through enhancer-mediated mechanisms. HLA zygosity analysis showed that homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of HCC (P = 0.10) and the risk was more pronounced in the older age group (age ≥50, P = 0.03). Discussion Our findings further the understanding of the genetic basis for HBV-related HCC predisposition in chronic HBV carriers.

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Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer

Cited by 18 publications

References 23 publications

The Evolving Epidemiology of Nasopharyngeal Carcinoma

The Evolving Epidemiology of Nasopharyngeal Carcinoma

Association Between Human Leukocyte Antigen Class I and II Diversity and Non-virus-associated Solid Tumors

Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese

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