PMID- 33272927
OWN - NLM
STAT- MEDLINE
DCOM- 20210512
LR  - 20240324
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 81
IP  - 4
DP  - 2021 Feb 15
TI  - Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer.
PG  - 1148-1152
LID - 10.1158/0008-5472.CAN-20-2292 [doi]
AB  - Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, 
      particularly those with infectious etiology or hematopoietic origin, given its 
      role in immune presentation. Previous studies focused primarily on HLA 
      allele/haplotype-specific associations. To answer whether associations are driven 
      by HLA class I (essential for T-cell cytotoxicity) or class II (important for 
      T-cell helper responses) genes, we analyzed GWAS from 24 case-control studies and 
      consortia comprising 27 cancers (totaling >71,000 individuals). Associations for 
      most cancers with infectious etiology or of hematopoietic origin were driven by 
      multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses 
      are important. Notable exceptions were observed for nasopharyngeal carcinoma, an 
      EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers 
      were associated with HLA class I region only and HLA class II region only, 
      implying the importance of cytotoxic T-cell responses for the former and CD4(+) 
      T-cell helper responses for the latter. Our findings suggest that increased 
      understanding of the pattern of HLA associations for individual cancers could 
      lead to better insights into specific mechanisms involved in cancer pathogenesis. 
      SIGNIFICANCE: GWAS of >71,000 individuals across 27 cancer types suggest that 
      patterns of HLA Class I and Class II associations may provide etiologic insights 
      for cancer.
CI  - (c)2020 American Association for Cancer Research.
FAU - Liu, Zhiwei
AU  - Liu Z
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland. zhiwei.liu@nih.gov.
FAU - Derkach, Andriy
AU  - Derkach A
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer 
      Center, New York, New York.
FAU - Yu, Kelly J
AU  - Yu KJ
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
FAU - Yeager, Meredith
AU  - Yeager M
AD  - Division of Cancer Epidemiology and Genetics, Cancer Genomics Research 
      Laboratory, National Cancer Institute, Bethesda, Maryland.
AD  - Frederick National Laboratory for Cancer Research, Frederick, Maryland.
FAU - Chang, Yu-Sun
AU  - Chang YS
AD  - Department of Microbiology and Immunology and Molecular Medicine Research Center, 
      Chang Gung University, Taoyuan, Taiwan.
AD  - Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, 
      Lin-Kou, Taiwan.
FAU - Chen, Chien-Jen
AU  - Chen CJ
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
FAU - Gyllensten, Ulf
AU  - Gyllensten U
AD  - Department of Immunology, Genetics and Pathology, Science for Life Laboratory 
      Uppsala, Uppsala University, Uppsala, Sweden.
FAU - Lan, Qing
AU  - Lan Q
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
FAU - Lee, Mei-Hsuan
AU  - Lee MH
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - McKay, James D
AU  - McKay JD
AD  - International Agency for Research on Cancer, World Health Organization, Lyon, 
      France.
FAU - Rothman, Nathaniel
AU  - Rothman N
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
FAU - Yang, Hwai-I
AU  - Yang HI
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan.
FAU - Hildesheim, Allan
AU  - Hildesheim A
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
FAU - Pfeiffer, Ruth M
AU  - Pfeiffer RM
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Rockville, Maryland.
LA  - eng
GR  - 001/WHO_/World Health Organization/International
GR  - ZIA CP010211/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20201203
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/genetics
MH  - Haplotypes
MH  - Hematologic Neoplasms/classification/epidemiology/genetics
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Male
MH  - Neoplasms/classification/epidemiology/*genetics/pathology
MH  - Tumor Virus Infections/classification/epidemiology/genetics/pathology
PMC - PMC9986718
MID - NIHMS1653488
COIS- Potential conflict of interest: All authors declare no conflict of interest.
EDAT- 2020/12/05 06:00
MHDA- 2021/05/13 06:00
PMCR- 2023/03/06
CRDT- 2020/12/04 05:37
PHST- 2020/07/09 00:00 [received]
PHST- 2020/10/26 00:00 [revised]
PHST- 2020/11/30 00:00 [accepted]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/05/13 06:00 [medline]
PHST- 2020/12/04 05:37 [entrez]
PHST- 2023/03/06 00:00 [pmc-release]
AID - 0008-5472.CAN-20-2292 [pii]
AID - 10.1158/0008-5472.CAN-20-2292 [doi]
PST - ppublish
SO  - Cancer Res. 2021 Feb 15;81(4):1148-1152. doi: 10.1158/0008-5472.CAN-20-2292. Epub 
      2020 Dec 3.