Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

作者：Aida Ferreiro-Iglesias, Corina Lesseur, James McKay, Rayjean J. Hung, Younghun Han, Xuchen Zong, David C. Christiani, Mattias Johansson, Xiangjun Xiao, Yafang Li, David C. Qian, Xuemei Ji, Geoffrey Liu, Neil E. Caporaso, Ghislaine Scélo, Давид Заридзе, Anush Mukeriya, Milica Kontić, Simona Ognjanovic, Jolanta Lissowska, Małgorzata Szołkowska, Beata Świątkowska, Vladimí­r Janout, Ivana Holcátová, Ciprian Bolca, Milan Savić, Miodrag Ognjanovic, Stig E. Bojesen, Xifeng Wu, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardón, Ana Fernández‐Somoano, Guillermo Fernández‐Tardón, Loı̈c Le Marchand, Gad Rennert, Chu Chen, Jennifer A. Doherty, Gary E. Goodman, Heike Bickeböller, H‐Erich Wichmann, Angela Risch, Albert Rosenberger, Hongbing Shen, Juncheng Dai, John K. Field, Michael P.A. Davies, Penella J. Woll, M. Dawn Teare, Lambertus A. Kiemeney, Erik H.F.M. van der Heijden, Jian‐Min Yuan, Yun‐Chul Hong, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Ming‐Sound Tsao, Mikael Johansson, Kjell Grankvist, Matthew B. Schabath, Angeline S. Andrew, Eric J. Duell, Olle Melander, Hans Brunnström, Philip Lazarus, Susanne M. Arnold, Stacey Slone, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Maria Teresa Landi, Christopher I. Amos, Paul Brennan · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-05890-2 · 被引用次数：59 · 研究领域：T-cell and B-cell Immunology、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

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.