PMID- 37148584
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20230619
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 92
DP  - 2023 Jun
TI  - Association of HLA diversity with the risk of 25 cancers in the UK Biobank.
PG  - 104588
LID - S2352-3964(23)00153-6 [pii]
LID - 10.1016/j.ebiom.2023.104588 [doi]
LID - 104588
AB  - BACKGROUND: The human leukocyte antigen (HLA) is a highly polymorphic region, and 
      HLA diversity may play a role in presenting tumour-associated peptides and 
      inducing immune responses. However, the effect of HLA diversity on cancers has 
      not been fully assessed. We aimed to explore the role of HLA diversity on cancer 
      development. METHODS: A pan-cancer analysis was performed to evaluate the effect 
      of HLA diversity, measured by HLA heterozygosity and HLA evolutionary divergence 
      (HED), on the susceptibility of 25 cancers in the UK Biobank. FINDINGS: We 
      observed that the diversity of HLA class II locus was associated with a lower 
      risk of lung cancer (OR(hetero) = 0.94, 95% CI = 0.90-0.97, P = 1.29 x 10(-4)) 
      and head and neck cancer (OR(hetero) = 0.91, 95% CI = 0.86-0.96, 
      P = 1.56 x 10(-3)). Besides, a lower risk of non-Hodgkin lymphoma was associated 
      with an increased diversity of HLA class I (OR(hetero) = 0.92, 95% CI = 
      0.87-0.98, P = 8.38 x 10(-3)) and class II locus (OR(hetero) = 0.89, 95% CI = 
      0.86-0.92, P = 1.65 x 10(-10)). A lower risk of Hodgkin lymphoma was associated 
      with the HLA class I diversity (OR(hetero) = 0.85, 95% CI = 0.75-0.96, P = 
      0.011). The protective effect of HLA diversity was mainly observed in 
      pathological subtypes with higher tumour mutation burden, such as lung squamous 
      cell carcinoma (P = 9.39 x 10(-3)) and diffuse large B cell lymphoma (P(class 
      I) = 4.12 x 10(-4); P(class Ⅱ) = 4.71 x 10(-5)), as well as the smoking subgroups 
      of lung cancer (P = 7.45 x 10(-5)) and head and neck cancer (P = 4.55 x 10(-3)). 
      INTERPRETATION: We provided a systematic insight into the effect of HLA diversity 
      on cancers, which might help to understand the etiological role of HLA on cancer 
      development. FUNDING: This study was supported by grants from the National 
      Natural Science Foundation of China (82273705, 82003520); the Basic and Applied 
      Basic Research Foundation of Guangdong Province, China (2021B1515420007); the 
      Science and Technology Planning Project of Guangzhou, China (201804020094); 
      Sino-Sweden Joint Research Programme (81861138006); the National Natural Science 
      Foundation of China (81973131, 81903395, 81803319, 81802708).
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Wang, Qiao-Ling
AU  - Wang QL
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; 
      School of Public Health, Sun Yat-sen University, Guangzhou, China.
FAU - Wang, Tong-Min
AU  - Wang TM
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China. 
      Electronic address: wangtm@sysucc.org.cn.
FAU - Deng, Chang-Mi
AU  - Deng CM
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Zhang, Wen-Li
AU  - Zhang WL
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - He, Yong-Qiao
AU  - He YQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Xue, Wen-Qiong
AU  - Xue WQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Liao, Ying
AU  - Liao Y
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Yang, Da-Wei
AU  - Yang DW
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; 
      School of Public Health, Sun Yat-sen University, Guangzhou, China.
FAU - Zheng, Mei-Qi
AU  - Zheng MQ
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Jia, Wei-Hua
AU  - Jia WH
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China; 
      School of Public Health, Sun Yat-sen University, Guangzhou, China. Electronic 
      address: jiawh@sysucc.org.cn.
LA  - eng
PT  - Journal Article
DEP - 20230504
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - Biological Specimen Banks
MH  - Genetic Predisposition to Disease
MH  - Histocompatibility Antigens Class I/genetics
MH  - Histocompatibility Antigens Class II/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - *Lung Neoplasms/etiology/genetics
MH  - HLA Antigens/genetics
MH  - United Kingdom/epidemiology
PMC - PMC10189092
OTO - NOTNLM
OT  - Cancer susceptibility
OT  - HLA evolutionary Divergence
OT  - HLA heterozygosity
OT  - UK Biobank
COIS- Declaration of interests The authors declare no potential conflicts of interest.
EDAT- 2023/05/06 19:42
MHDA- 2023/06/19 13:08
PMCR- 2023/05/04
CRDT- 2023/05/06 18:01
PHST- 2023/01/05 00:00 [received]
PHST- 2023/03/17 00:00 [revised]
PHST- 2023/04/11 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/05/06 19:42 [pubmed]
PHST- 2023/05/06 18:01 [entrez]
PHST- 2023/05/04 00:00 [pmc-release]
AID - S2352-3964(23)00153-6 [pii]
AID - 104588 [pii]
AID - 10.1016/j.ebiom.2023.104588 [doi]
PST - ppublish
SO  - EBioMedicine. 2023 Jun;92:104588. doi: 10.1016/j.ebiom.2023.104588. Epub 2023 May 
      4.