Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci
Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC...
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Published in | Communications biology Vol. 3; no. 1; p. 759 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
11.12.2020
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC pathogenesis remain elusive. Our large-scale comprehensive MHC region deep sequencing study of 5689 Hong Kong Chinese identifies eight independent NPC-associated signals and provides mechanistic insight for disrupted transcription factor binding, altering target gene transcription. Two novel protective variants, rs2517664 (
T
rs2517664
= 4.6%,
P
= 6.38 × 10
−21
) and rs117495548 (
G
rs117495548
= 3.0%,
P
= 4.53 × 10
−13
), map near
TRIM31
and
TRIM39
/
TRIM39-RPP21
; multiple independent protective signals map near
HLA-B
including a previously unreported variant, rs2523589 (
P
= 1.77 × 10
−36
). The rare
HLA-B*07:05
allele (OR < 0.015,
P
= 5.83 × 10
−21
) is absent in NPC, but present in controls. The most prevalent haplotype lacks seven independent protective alleles (OR = 1.56) and the one with additional Asian-specific susceptibility rs9391681 allele (OR = 2.66) significantly increased NPC risk. Importantly, this study provides new evidence implicating two non-human leukocyte antigen (HLA) genes, E3 ubiquitin ligases,
TRIM31
and
TRIM39
, impacting innate immune responses, with NPC risk reduction, independent of classical HLA class I/II alleles.
Here the authors report a major histocompatibility complex (MHC) association analysis for nasopharyngeal carcinoma in Chinese individuals from Hong Kong, finding 8 independent associated loci associated with lower risk for developing nasopharyngeal carcinoma. Two non-human leukocyte antigen (HLA) genes are E3 ubiquitin ligases,
TRIM31
and
TRIM39
, having a role in the innate immune response and implicating the importance of host Epstein-Barr virus interactions in this cancer. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2399-3642 2399-3642 |
DOI: | 10.1038/s42003-020-01487-y |