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

• DOI: 10.1038/s41467-018-05890-2
• Publication Date: 2018-09-19T16:20:23Z
• Authors: Aida Ferreiro-Igl...; Corina Lesseur; James McKay; Rayjean J. Hung; Younghun Han; Xuchen Zong; David Christiani; Mattias Johansson; Xiangjun Xiao; Yafang Li; David C. Qian; Xuemei Ji; Geoffrey Liu; Neil Caporaso; Ghislaine Scelo; David Zaridze; Anush Mukeriya; Milica Kontic; Simona Ognjanovic; Jolanta Lissowska; Małgorzata Szołko...; Beata Swiatkowska; Vladimir Janout; Ivana Holcatova; Ciprian Bolca; Milan Savic; Miodrag Ognjanovic; Stig Egil Bojesen; Xifeng Wu; Demetrios Albanes; Melinda C. Aldrich; Adonina Tardon; Ana Fernandez-Som...; Guillermo Fernand...; Loic Le Marchand; Gadi Rennert; Chu Chen; Jennifer Doherty; Gary Goodman; Heike Bickeböller; H-Erich Wichmann; Angela Risch; Albert Rosenberger; Hongbing Shen; Juncheng Dai; John K. Field; Michael Davies; Penella Woll; M. Dawn Teare; Lambertus A. Kiem...; Erik H. F. M. van...; Jian-Min Yuan; Yun-Chul Hong; Aage Haugen; Shanbeh Zienolddiny; Stephen Lam; Ming-Sound Tsao; Mikael Johansson; Kjell Grankvist; Matthew B. Schabath; Angeline Andrew; Eric Duell; Olle Melander; Hans Brunnström; Philip Lazarus; Susanne Arnold; Stacey Slone; Jinyoung Byun; Ahsan Kamal; Dakai Zhu; Maria Teresa Landi; Christopher I. Amos; Paul Brennan
• Keywords: Lung cancer susceptibility; SNP

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