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 inCommunications biology Vol. 3; no. 1; p. 759
Main Authors Ning, Lvwen, Ko, Josephine Mun-Yee, Yu, Valen Zhuoyou, Ng, Hoi Yan, Chan, Candy King-Chi, Tao, Lihua, Lam, Shiu-Yeung, Leong, Merrin Man-Long, Ngan, Roger Kai-Cheong, Kwong, Dora Lai-Wan, Lee, Anne Wing-Mui, Ng, Wai-Tong, Cheng, Ashley, Tung, Stewart, Lee, Victor Ho-Fun, Lam, Ka-On, Kwan, Chung-Kong, Li, Wing-Sum, Yau, Stephen, Bei, Jin-Xin, Lung, Maria Li
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 11.12.2020
Nature Publishing Group
Nature Portfolio
Subjects
45/23
631/208/69
631/250/248
631/67/69
692/699/67/1536
82/51
82/80
Alleles
Antigens
Association analysis
Biology
Biomedical and Life Sciences
Epstein-Barr virus
Haplotypes
Histocompatibility antigen HLA
Immune response
Innate immunity
Life Sciences
Major histocompatibility complex
Nasopharyngeal carcinoma
Ubiquitin
Ubiquitin-protein ligase
Hong Kong China
China
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Abstract 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.
AbstractList Abstract 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.
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.
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.
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  = 4.6%, P = 6.38 × 10 ) and rs117495548 (G  = 3.0%, P = 4.53 × 10 ), 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 ). The rare HLA-B*07:05 allele (OR < 0.015, P = 5.83 × 10 ) 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.
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 (Trs2517664 = 4.6%, P = 6.38 × 10−21) and rs117495548 (Grs117495548 = 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.
ArticleNumber 759
Author Kwong, Dora Lai-Wan
Lee, Victor Ho-Fun
Kwan, Chung-Kong
Lam, Shiu-Yeung
Cheng, Ashley
Tung, Stewart
Ngan, Roger Kai-Cheong
Bei, Jin-Xin
Ning, Lvwen
Ng, Wai-Tong
Lung, Maria Li
Tao, Lihua
Li, Wing-Sum
Leong, Merrin Man-Long
Yau, Stephen
Lee, Anne Wing-Mui
Chan, Candy King-Chi
Lam, Ka-On
Yu, Valen Zhuoyou
Ko, Josephine Mun-Yee
Ng, Hoi Yan
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  organization: Department of Clinical Oncology, University of Hong Kong
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  organization: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Department of Oncology, Princess Margaret Hospital
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  organization: Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy
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  email: mlilung@hku.hk
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33311639$$D View this record in MEDLINE/PubMed
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PublicationTitleAbbrev Commun Biol
PublicationTitleAlternate Commun Biol
PublicationYear 2020
Publisher Nature Publishing Group UK
Nature Publishing Group
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
– name: Nature Portfolio
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SSID ssj0001999634
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Snippet Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC...
Abstract Despite pronounced associations of major histocompatibility complex (MHC) regions with nasopharyngeal carcinoma (NPC), causal variants underlying NPC...
Here the authors report a major histocompatibility complex (MHC) association analysis for nasopharyngeal carcinoma in Chinese individuals from Hong Kong,...
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SubjectTerms 45/23
631/208/69
631/250/248
631/67/69
692/699/67/1536
82/51
82/80
Alleles
Antigens
Association analysis
Biology
Biomedical and Life Sciences
Epstein-Barr virus
Haplotypes
Histocompatibility antigen HLA
Immune response
Innate immunity
Life Sciences
Major histocompatibility complex
Nasopharyngeal carcinoma
Ubiquitin
Ubiquitin-protein ligase
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Title Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci
URI https://link.springer.com/article/10.1038/s42003-020-01487-y
https://www.ncbi.nlm.nih.gov/pubmed/33311639
https://www.proquest.com/docview/2473310044
https://search.proquest.com/docview/2470029400
https://pubmed.ncbi.nlm.nih.gov/PMC7733486
https://doaj.org/article/f82cb968f4d947bb91dd4a6ed21c1e75
Volume 3
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