Nature Communications (Sep 2018)
Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
- Aida Ferreiro-Iglesias,
- 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 Szołkowska,
- 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-Somoano,
- Guillermo Fernandez-Tardon,
- 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. 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 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
Affiliations
- Aida Ferreiro-Iglesias
- International Agency for Research on Cancer, World Health Organization
- Corina Lesseur
- International Agency for Research on Cancer, World Health Organization
- James McKay
- International Agency for Research on Cancer, World Health Organization
- Rayjean J. Hung
- Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto
- Younghun Han
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Xuchen Zong
- Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto
- David Christiani
- Department of Environmental Health, Harvard TH Chan School of Public Health, Massachusetts General Hospital/ Harvard Medical School
- Mattias Johansson
- International Agency for Research on Cancer, World Health Organization
- Xiangjun Xiao
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Yafang Li
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- David C. Qian
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Xuemei Ji
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Geoffrey Liu
- Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto
- Neil Caporaso
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Ghislaine Scelo
- International Agency for Research on Cancer, World Health Organization
- David Zaridze
- Russian N.N. Blokhin Cancer Research Centre
- Anush Mukeriya
- Russian N.N. Blokhin Cancer Research Centre
- Milica Kontic
- Clinical Center of Serbia
- Simona Ognjanovic
- International Organization for Cancer Prevention and Research
- Jolanta Lissowska
- M. Sklodowska-Curie Cancer Center, Institute of Oncology
- Małgorzata Szołkowska
- Department of Pathology, National Tuberculosis and Lung Diseases Research Institute
- Beata Swiatkowska
- Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine
- Vladimir Janout
- Faculty of Medicine, University of Olomouc
- Ivana Holcatova
- 2nd Faculty of Medicine, Institute of Public Health and Preventive Medicine, Charles University
- Ciprian Bolca
- Institute of Pneumology “Marius Nasta”
- Milan Savic
- Department of Thoracic Surgery Clinical Center of Serbia Belgrade
- Miodrag Ognjanovic
- International Organization for Cancer Prevention and Research
- Stig Egil Bojesen
- Copenhagen General Population Study, Herlev and Gentofte Hospital
- Xifeng Wu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center
- Demetrios Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Melinda C. Aldrich
- Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center
- Adonina Tardon
- University of Oviedo and CIBERESP, Faculty of Medicine
- Ana Fernandez-Somoano
- University of Oviedo and CIBERESP, Faculty of Medicine
- Guillermo Fernandez-Tardon
- University of Oviedo and CIBERESP, Faculty of Medicine
- Loic Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center
- Gadi Rennert
- Clalit National Cancer Control Center at Carmel Medical Center and Technion Faculty of Medicine
- Chu Chen
- Department of Epidemiology, University of Washington School of Public Health and Community Medicine
- Jennifer Doherty
- Department of Epidemiology, University of Washington School of Public Health and Community Medicine
- Gary Goodman
- Swedish Medical Group
- Heike Bickeböller
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen
- H-Erich Wichmann
- Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximilians University
- Angela Risch
- University of Salzburg and Cancer Cluster Salzburg
- Albert Rosenberger
- Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen
- Hongbing Shen
- Department of Epidemiology and Biostatistics, Jiangsu Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University
- Juncheng Dai
- Department of Epidemiology and Biostatistics, Jiangsu Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University
- John K. Field
- Institute of Translational Medicine, University of Liverpool
- Michael Davies
- Institute of Translational Medicine, University of Liverpool
- Penella Woll
- Department of Oncology, University of Sheffield
- M. Dawn Teare
- School of Health and Related Research, University Of Sheffield
- Lambertus A. Kiemeney
- Radboud University Medical Center
- Erik H. F. M. van der Heijden
- Radboud University Medical Center
- Jian-Min Yuan
- University of Pittsburgh Cancer Institute
- Yun-Chul Hong
- Department of Preventive Medicine, Seoul National University College of Medicine
- Aage Haugen
- National Institute of Occupational Health
- Shanbeh Zienolddiny
- National Institute of Occupational Health
- Stephen Lam
- British Columbia Cancer Agency
- Ming-Sound Tsao
- Princess Margaret Cancer Centre
- Mikael Johansson
- Department of Radiation Sciences, Umeå University
- Kjell Grankvist
- Department of Medical Biosciences, Umeå University
- Matthew B. Schabath
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute
- Angeline Andrew
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Eric Duell
- Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO‐IDIBELL)
- Olle Melander
- Department of Clinical Sciences Malmö, Lund University
- Hans Brunnström
- Laboratory Medicine Region Skåne, Department of Clinical Sciences Lund, Pathology, Lund University
- Philip Lazarus
- Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University
- Susanne Arnold
- University of Kentucky, Markey Cancer Center
- Stacey Slone
- University of Kentucky, Markey Cancer Center
- Jinyoung Byun
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Ahsan Kamal
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Dakai Zhu
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Maria Teresa Landi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- Christopher I. Amos
- Biomedical Data Science, Geisel School of Medicine at Dartmouth
- Paul Brennan
- International Agency for Research on Cancer, World Health Organization
- DOI
- https://doi.org/10.1038/s41467-018-05890-2
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 12
Abstract
Abstract 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.
