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Tan, T.* ; Shaw, V.R.* ; Byun, J.* ; Lee, H.S.* ; Han, Y.* ; Li, Y.* ; Hung, R.J.* ; Christiani, D.C.* ; Wang, X.A.* ; Johansson, M.* ; Xiao, X.* ; Zaridze, D.* ; Bojesen, S.E.* ; Shete, S.* ; Albanes, D.* ; Aldrich, M.C.* ; Tardon, A.* ; Fernandez-Tardon, G.* ; Le Marchand, L.* ; Rennert, G.* ; Bickeböller, H.* ; Wichmann, H.-E. ; Risch, A.* ; Field, J.K.* ; Davies, M.* ; Woll, P.* ; Kiemeney, L.A.* ; Haugen, A.* ; Zienolddiny, S.* ; Lam, S.* ; Johansson, M.* ; Grankvist, K.* ; Schabath, M.B.* ; Andrew, A.* ; Lazarus, P.* ; Arnold, S.M.* ; Zhu, D.* ; Landi, M.T.* ; McKay, J.* ; Amos, C.* ; Cheng, C.*

Germline HLA heterozygosity is associated with decreased lung cancer risk.

HGG Advances 7:100567 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Heterozygosity at human leukocyte antigen (HLA) loci may improve lung cancer immunosurveillance by increasing recognition of the tumor by the immune system. Previous studies utilizing data from population-level biobanks, such as the United Kingdom Biobank and FinnGen, have identified an association between germline HLA class-II heterozygosity and reduced lung cancer risk in smokers. In the present study, we evaluate the association between HLA heterozygosity and lung cancer in a large case-control study (15,302 cases; 14,580 controls) with imputed HLA allele-type information, comparing differences in HLA heterozygosity between smokers and non-smokers, amongst lung cancer subtypes, and at 2- and 4-digit HLA allele resolution. We identify a strong protective association of HLA-II heterozygosity in smokers compared to non-smokers, particularly at the HLA-DPB1 and HLA-DPA1 loci, and provide subtype-specific resolution. Finally, analysis of the additive effects of HLA allele heterozygosity in smokers identified significant associations with several 4-digit HLA alleles, including HLA-B*08:01, HLA-A*01:01, HLA-C*07:01, HLA-DQA1*05:01, HLA-DRB1*03:01, and HLA-C*03:04. Our study provides additional evidence, with added histologic subtype information, that germline HLA-II heterozygosity is inversely associated with lung cancer risk.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genetic Risk ; Genetics ; Hla ; Lung Cancer ; Smoking; Susceptibility Loci; Alleles
ISSN (print) / ISBN 2666-2477
e-ISSN 2666-2477
Journal Human Genetics and Genomics Advances
Quellenangaben Volume: 7, Issue: 2, Pages: , Article Number: 100567 Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants NIH S10 shared instrument
NCI of the NIH
Cancer Prevention Research Institute of Texas (CPRIT)
National Institutes of Health (NIH) National Cancer Institute (NCI)