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

The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cance...

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Veröffentlicht in:	Nature communications Jg. 9; H. 1; S. 3927 - 12
Hauptverfasser:	Ferreiro-Iglesias, Aida, Lesseur, Corina, McKay, James, Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Christiani, David, Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Qian, David C., Ji, Xuemei, Liu, Geoffrey, Caporaso, Neil, Scelo, Ghislaine, Zaridze, David, Mukeriya, Anush, Kontic, Milica, Ognjanovic, Simona, Lissowska, Jolanta, Szołkowska, Małgorzata, Swiatkowska, Beata, Janout, Vladimir, Holcatova, Ivana, Bolca, Ciprian, Savic, Milan, Ognjanovic, Miodrag, Bojesen, Stig Egil, Wu, Xifeng, Albanes, Demetrios, Aldrich, Melinda C., Tardon, Adonina, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, Le Marchand, Loic, Rennert, Gadi, Chen, Chu, Doherty, Jennifer, Goodman, Gary, Bickeböller, Heike, Wichmann, H-Erich, Risch, Angela, Rosenberger, Albert, Shen, Hongbing, Dai, Juncheng, Field, John K., Davies, Michael, Woll, Penella, Teare, M. Dawn, Kiemeney, Lambertus A., van der Heijden, Erik H. F. M., Yuan, Jian-Min, Hong, Yun-Chul, Haugen, Aage, Zienolddiny, Shanbeh, Lam, Stephen, Tsao, Ming-Sound, Johansson, Mikael, Grankvist, Kjell, Schabath, Matthew B., Andrew, Angeline, Duell, Eric, Melander, Olle, Brunnström, Hans, Lazarus, Philip, Arnold, Susanne, Slone, Stacey, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Landi, Maria Teresa, Amos, Christopher I., Brennan, Paul
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 25.09.2018 Nature Publishing Group Nature Portfolio
Schlagworte:	45/43 692/308/174 692/308/2056 Amino acids Asian People - genetics Cancer Cancer and Oncology Cancer och onkologi Chromosome Mapping Clinical Medicine Drb1 protein Female Gene Frequency Gene mapping Genes Genetic diversity Genetic Predisposition to Disease - ethnology Genetic Predisposition to Disease - genetics Genotype Health risks Histocompatibility antigen HLA HLA Antigens - genetics Humanities and Social Sciences Humans Klinisk medicin Loci Lung cancer Lung Neoplasms - ethnology Lung Neoplasms - genetics Major histocompatibility complex Major Histocompatibility Complex - genetics Male Medical and Health Sciences Medicin och hälsovetenskap Middle Aged Minority & ethnic groups multidisciplinary Peptides - genetics Polymorphism, Single Nucleotide Science Science (multidisciplinary) Single-nucleotide polymorphism White People - genetics
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Zusammenfassung:	The basis for associations between lung cancer and major histocompatibility complex genes is not completely understood. Here the authors further consider genetic variation within the MHC region in lung cancer patients and identify independent associations within HLA genes that explain MHC lung cancer associations in Europeans and Asian populations. 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-B0801 peptide binding groove and an independent HLA-DQB106 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB10401 and HLA-DRB10701 ; 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-018-05890-2