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 |
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Nature Publishing Group UK
11.12.2020
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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 |
Author_xml | – sequence: 1 givenname: Lvwen surname: Ning fullname: Ning, Lvwen organization: Department of Clinical Oncology, University of Hong Kong – sequence: 2 givenname: Josephine Mun-Yee orcidid: 0000-0002-7997-331X surname: Ko fullname: Ko, Josephine Mun-Yee email: joko@hku.hk organization: Department of Clinical Oncology, University of Hong Kong – sequence: 3 givenname: Valen Zhuoyou surname: Yu fullname: Yu, Valen Zhuoyou organization: Department of Clinical Oncology, University of Hong Kong – sequence: 4 givenname: Hoi Yan surname: Ng fullname: Ng, Hoi Yan organization: Department of Clinical Oncology, University of Hong Kong – sequence: 5 givenname: Candy King-Chi surname: Chan fullname: Chan, Candy King-Chi organization: Department of Clinical Oncology, University of Hong Kong – sequence: 6 givenname: Lihua surname: Tao fullname: Tao, Lihua organization: Department of Clinical Oncology, University of Hong Kong – sequence: 7 givenname: Shiu-Yeung orcidid: 0000-0003-3001-3112 surname: Lam fullname: Lam, Shiu-Yeung organization: Department of Clinical Oncology, University of Hong Kong – sequence: 8 givenname: Merrin Man-Long surname: Leong fullname: Leong, Merrin Man-Long organization: Department of Clinical Oncology, University of Hong Kong – sequence: 9 givenname: Roger Kai-Cheong surname: Ngan fullname: Ngan, Roger Kai-Cheong organization: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Department of Clinical Oncology, Queen Elizabeth Hospital – sequence: 10 givenname: Dora Lai-Wan surname: Kwong fullname: Kwong, Dora Lai-Wan organization: Department of Clinical Oncology, University of Hong Kong, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong – sequence: 11 givenname: Anne Wing-Mui surname: Lee fullname: Lee, Anne Wing-Mui organization: Department of Clinical Oncology, University of Hong Kong, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong – sequence: 12 givenname: Wai-Tong surname: Ng fullname: Ng, Wai-Tong organization: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital – sequence: 13 givenname: Ashley surname: Cheng fullname: Cheng, Ashley organization: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Department of Oncology, Princess Margaret Hospital – sequence: 14 givenname: Stewart orcidid: 0000-0002-2527-6471 surname: Tung fullname: Tung, Stewart organization: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Department of Clinical Oncology, Tuen Mun Hospital – sequence: 15 givenname: Victor Ho-Fun surname: Lee fullname: Lee, Victor Ho-Fun organization: Department of Clinical Oncology, University of Hong Kong, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong – sequence: 16 givenname: Ka-On orcidid: 0000-0002-7523-5088 surname: Lam fullname: Lam, Ka-On organization: Department of Clinical Oncology, University of Hong Kong, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong – sequence: 17 givenname: Chung-Kong surname: Kwan fullname: Kwan, Chung-Kong organization: Department of Clinical Oncology, Queen Elizabeth Hospital – sequence: 18 givenname: Wing-Sum surname: Li fullname: Li, Wing-Sum organization: Department of Clinical Oncology, Queen Elizabeth Hospital – sequence: 19 givenname: Stephen surname: Yau fullname: Yau, Stephen organization: Department of Clinical Oncology, Queen Elizabeth Hospital – sequence: 20 givenname: Jin-Xin orcidid: 0000-0003-1333-407X surname: Bei fullname: Bei, Jin-Xin 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 – sequence: 21 givenname: Maria Li surname: Lung fullname: Lung, Maria Li email: mlilung@hku.hk organization: Department of Clinical Oncology, University of Hong Kong, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33311639$$D View this record in MEDLINE/PubMed |
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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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Title | Nasopharyngeal carcinoma MHC region deep sequencing identifies HLA and novel non-HLA TRIM31 and TRIM39 loci |
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