Aida Ferreiro-Iglesias, World Health Organization, France
Corina Lesseur, World Health Organization, France
James McKay, World Health Organization, France
Rayjean J. Hung, University of Toronto, Canada
Younghun Han, Dartmouth College
Xuchen Zong, University of Toronto, Canada
David Christiani, Harvard University
Mattias Johansson, World Health Organization, France
Xiangjun Xiao, Dartmouth College
Yafang Li, Dartmouth College
David C. Qian, Dartmouth College
Xuemei Ji, Dartmouth College
Geoffrey Liu, University of Toronto, Canada
Neil Caporaso, National Institutes of Health
Ghislaine Scelo, World Health Organization, France
David Zaridze, Russian N. N. Blokhin Cancer Research Centre, Russia
Anush Mukeriya, Russian N. N. Blokhin Cancer Research Centre, Russia
Milica Kontic, Clinical Center of Serbia, Serbia
Simona Ognjanovic, International Organization for Cancer Prevention and Research, Serbia
Jolanta Lissowska, Institute of Oncology, Poland
Małgorzata Szołkowska, National Tuberculosis and Lung Diseases Research Institute, Poland
Beata Swiatkowska, Nofer Institute of Occupational Medicine, Poland
Vladimir Janout, University of Olomouc, Czech Republic
Ivana Holcatova, Charles University, Czech Republic
Ciprian Bolca, Institute of Pneumology “Marius Nasta”, Romania
Milan Savic, Clinical Center of Serbia, Serbia
Miodrag Ognjanovic, International Organization for Cancer Prevention and Research, Serbia
Stig Egil Bojesen, Herlev and Gentofte Hospital, Denmark
Xifeng Wu, The University of Texas MD Anderson Cancer Center
Demetrios Albanes, National Institutes of Health
Susanne M. Arnold, University of KentuckyFollow


Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA–tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

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Notes/Citation Information

Published in Nature Communications, v. 9, article no. 3927, p. 1-12.

© The Author(s) 2018

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article or visit:

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Funding Information

Transdisciplinary Research for Cancer in Lung (TRICL) research team of the International Lung Cancer Consortium (ILCCO) was supported by (U19-CA148127 and CA148127S1). The ILCCO data harmonization is supported by Cancer Care Ontario Research Chair of Population Studies to R. H. and Lunenfeld-Tanenbaum Research Institute, Sinai Health System. TRICL-ILCCO Oncoarray was supported by in-kind genotyping Centre for Inherited Disease Research (26820120008i-0-26800068-1).

Due to the large number of funding sources, only the first few are listed in this section. For the complete list of funding sources, please download this article.

Related Content

Genotype data for the lung cancer OncoArray study have been deposited at the database of Genotypes and Phenotypes (dbGaP) under accession phs001273.v1.p1. The Asian replication dataset was downloaded from dbGaP under accession phs000716.v1.p1.

Supplementary Information accompanies this paper at

41467_2018_5890_MOESM1_ESM.pdf (2253 kB)
Supplementary Information

41467_2018_5890_MOESM2_ESM.pdf (414 kB)
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