Journal Article

DKFZ-2026-00113

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Germline HLA heterozygosity is associated with decreased lung cancer risk.

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.DKFZ* ; 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.

2026
Cell Press Cambridge, Ma.

Abstract: 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.

Note: epub

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Contributing Institute(s):

1. Epigenomik (B370)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Emerging Sources Citation Index ; Fees ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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