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

doi:10.1038/s41467-018-05890-2

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

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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.

Original language	English
Article number	3927
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05890-2
State	Published - Dec 1 2018

Bibliographical note

Publisher Copyright:
© 2018, © 2018, The Author(s).

Funding

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). CAPUA study was supported by FIS-FEDER/Spain grant numbers FIS-01/310, FIS-PI03-0365, and FIS-07-BI060604, FICYT/Asturias grant numbers FICYT PB02-67 and FICYT IB09-133, and the University Institute of Oncology (IUOPA), of the University of Oviedo and the Ciber de Epidemiología y Salud Pública. CIBERESP, SPAIN. The work performed in the CARET study was supported by the The National Institute of Health/ National Cancer Institute: UM1 CA167462 (PI: Goodman), National Institute of Health UO1‐CA6367307 (PIs Omen, Goodman); National Institute of Health R01 CA111703 (PI Chen), National Institute of Health 5R01 CA15198901A1(PI Doherty). Norway study was supported by Norwegian Cancer Society, Norwegian Research Council The NELCS study: Grant Number P20RR018787 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The Liverpool Lung project is supported by the Roy Castle Lung Cancer Foundation. The Harvard Lung Cancer Study was supported by the NIH (National Cancer Institute) grants CA092824, CA090578, CA074386. The Multiethnic Cohort Study was partially supported by NIH Grants CA164973, CA033619, CA63464 and CA148127. The work performed in MSH-PMH study was supported by The Canadian Cancer Society Research Institute (020214), Ontario Institute of Cancer and Cancer Care Ontario Chair Award to RJH and GL and the Alan Brown Chair and Lusi Wong Programs at the Princess Margaret Hospital Foundation. NJLCS work was funded by the State Key Program of National Natural Science of China (81230067), the National Key Basic Research Program Grant (2011CB503805), the Major Program of the National Natural Science Foundation of China (81390543). Tampa Lung Cancer Study (Tampa) was supported by National Institutes of Health: R01 DE013158, PO1 CA68384 and R01 ES025460. The Shanghai Cohort Study (SCS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). The Singapore Chinese Health Study (SCHS) was supported by National Institutes of Health R01 CA144034 (PI: Yuan) and UM1 CA182876 (PI: Yuan). TCL work has been supported in part the James & Esther King Biomedical Research Program (09KN-15), National Institutes of Health Specialized Programs of Research Excellence (SPORE) Grant (P50 CA119997), and by a Cancer Center Support Grant (CCSG) at the H. Lee Moffitt Cancer Center and Research Institute, an NCI designated Comprehensive Cancer Center (grant number P30-CA76292). The Vanderbilt Lung Cancer Study – BioVU dataset used for the analyses described was obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the Vanderbilt CTSA grant UL1TR000445 from NCATS/NIH. Dr. Aldrich was supported by NIH/National Cancer Institute K07CA172294 (PI: Aldrich) and Dr. Bush was supported by NHGRI/NIH U01HG004798 (PI: Crawford). The L2 study. Lung cancer cases and controls were recruited through a multicentric case-control study coordinated by the International Agency for Research on Cancer in Russia, Poland, Serbia, Czech Republic, and Romania from 2005 to 2013. Cases were incident cancer patients collected from general hospitals. Controls were recruited from individuals visiting general hospitals and out-patient clinics for disorders unrelated to lung cancer and/or its associated risk factors, or from the general population. Information on lifestyle risk factors, medical and family history was collected from subjects by interview using a standard questionnaire. All study participants provided written informed consent. The current study included 1,133 lung cancer cases and 1,117 controls genotyped on the Oncoarray. The study in Lodz center was partially funded by Nofer Institute of Occupational Medicine, under task NIOM 10.13: Predictors of mortality from non-small cell lung cancer - field study.

Funders	Funder number
Hospital Universitario Central de Asturias- Oviedo and Instituto de Investigación Biosanitaria del Principado de Asturias	FICYT IB09-133, FICYT PB02-67
Markey Cancer Center's Cancer Center Support
Ciber de Epidemiología y Salud Pública
IUOPA
James and Esther King Florida Biomedical Research Program	09KN-15, P50 CA119997
Lunenfeld-Tanenbaum Research Institute
National Institute of Health UO1‐CA6367307	5R01 CA15198901A1, R01 CA111703
Sinai Health System (Toronto)	FIS-PI03-0365, FIS-01/310, 26820120008i-0-26800068-1, FIS-07-BI060604
University Institute of Oncology
National Institutes of Health (NIH)
National Human Genome Research Institute	U01HG004798
National Childhood Cancer Registry – National Cancer Institute	P30-CA76292, K07CA172294, R01CA074386
National Center for Research Resources	P20RR018787
H Lee Moffitt Cancer Center and Research Institute Hospital
National Center for Advancing Translational Sciences (NCATS)	UL1TR000445
Kreftforeningen
Roy Castle Lung Cancer Foundation	CA164973, CA148127, CA092824, CA074386, CA63464, CA090578, CA033619
Princess Margaret Hospital Foundation
Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center	1S10RR025141-01
Canadian Cancer Society Research Institute	020214
National Natural Science Foundation of China (NSFC)	R01 CA144034, 81230067, PO1 CA68384, UM1 CA182876, R01 DE013158, 81390543, R01 ES025460
Norges Forskningsråd
Institut National Du Cancer	UM1 CA167462
Universidad de Oviedo
National Key Basic Research and Development Program of China	2011CB503805
Instytut Medycyny Pracy im. prof. J. Nofera

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

Access to Document

10.1038/s41467-018-05890-2

Cite this

Ferreiro-Iglesias, A., Lesseur, C., McKay, J., Hung, R. J., Han, Y., Zong, X., Christiani, D., Johansson, M., Xiao, X., Li, Y., Qian, D. C., Ji, X., Liu, G., Caporaso, N., Scelo, G., Zaridze, D., Mukeriya, A., Kontic, M., Ognjanovic, S., ... Brennan, P. (2018). Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity. Nature Communications, 9(1), Article 3927. https://doi.org/10.1038/s41467-018-05890-2

@article{6ffa7d6324e24706b1d9e95dda3461ce,

title = "Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity",

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.",

author = "Aida Ferreiro-Iglesias and Corina Lesseur and James McKay and Hung, \{Rayjean J.\} and Younghun Han and Xuchen Zong and David Christiani and Mattias Johansson and Xiangjun Xiao and Yafang Li and Qian, \{David C.\} and Xuemei Ji and Geoffrey Liu and Neil Caporaso and Ghislaine Scelo and David Zaridze and Anush Mukeriya and Milica Kontic and Simona Ognjanovic and Jolanta Lissowska and Ma{\l}gorzata Szo{\l}kowska and Beata Swiatkowska and Vladimir Janout and Ivana Holcatova and Ciprian Bolca and Milan Savic and Miodrag Ognjanovic and Bojesen, \{Stig Egil\} and Xifeng Wu and Demetrios Albanes and Aldrich, \{Melinda C.\} and Adonina Tardon and Ana Fernandez-Somoano and Guillermo Fernandez-Tardon and \{Le Marchand\}, Loic and Gadi Rennert and Chu Chen and Jennifer Doherty and Gary Goodman and Heike Bickeb{\"o}ller and Wichmann, \{H. Erich\} and Angela Risch and Albert Rosenberger and Hongbing Shen and Juncheng Dai and Field, \{John K.\} and Michael Davies and Penella Woll and Teare, \{M. Dawn\} and Kiemeney, \{Lambertus A.\} and \{van der Heijden\}, \{Erik H.F.M.\} and Yuan, \{Jian Min\} and Hong, \{Yun Chul\} and Aage Haugen and Shanbeh Zienolddiny and Stephen Lam and Tsao, \{Ming Sound\} and Mikael Johansson and Kjell Grankvist and Schabath, \{Matthew B.\} and Angeline Andrew and Eric Duell and Olle Melander and Hans Brunnstr{\"o}m and Philip Lazarus and Susanne Arnold and Stacey Slone and Jinyoung Byun and Ahsan Kamal and Dakai Zhu and Landi, \{Maria Teresa\} and Amos, \{Christopher I.\} and Paul Brennan",

note = "Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-05890-2",

language = "English",

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Ferreiro-Iglesias, A, Lesseur, C, McKay, J, Hung, RJ, Han, Y, Zong, X, Christiani, D, Johansson, M, Xiao, X, Li, Y, Qian, DC, Ji, X, Liu, G, Caporaso, N, Scelo, G, Zaridze, D, Mukeriya, A, Kontic, M, Ognjanovic, S, Lissowska, J, Szołkowska, M, Swiatkowska, B, Janout, V, Holcatova, I, Bolca, C, Savic, M, Ognjanovic, M, Bojesen, SE, Wu, X, Albanes, D, Aldrich, MC, Tardon, A, Fernandez-Somoano, A, Fernandez-Tardon, G, Le Marchand, L, Rennert, G, Chen, C, Doherty, J, Goodman, G, Bickeböller, H, Wichmann, HE, Risch, A, Rosenberger, A, Shen, H, Dai, J, Field, JK, Davies, M, Woll, P, Teare, MD, Kiemeney, LA, van der Heijden, EHFM, Yuan, JM, Hong, YC, Haugen, A, Zienolddiny, S, Lam, S, Tsao, MS, Johansson, M, Grankvist, K, Schabath, MB, Andrew, A, Duell, E, Melander, O, Brunnström, H, Lazarus, P, Arnold, S, Slone, S, Byun, J, Kamal, A, Zhu, D, Landi, MT, Amos, CI & Brennan, P 2018, 'Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity', Nature Communications, vol. 9, no. 1, 3927. https://doi.org/10.1038/s41467-018-05890-2

TY - JOUR

T1 - Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

AU - Ferreiro-Iglesias, Aida

AU - Lesseur, Corina

AU - McKay, James

AU - Hung, Rayjean J.

AU - Han, Younghun

AU - Zong, Xuchen

AU - Christiani, David

AU - Johansson, Mattias

AU - Xiao, Xiangjun

AU - Li, Yafang

AU - Qian, David C.

AU - Ji, Xuemei

AU - Liu, Geoffrey

AU - Caporaso, Neil

AU - Scelo, Ghislaine

AU - Zaridze, David

AU - Mukeriya, Anush

AU - Kontic, Milica

AU - Ognjanovic, Simona

AU - Lissowska, Jolanta

AU - Szołkowska, Małgorzata

AU - Swiatkowska, Beata

AU - Janout, Vladimir

AU - Holcatova, Ivana

AU - Bolca, Ciprian

AU - Savic, Milan

AU - Ognjanovic, Miodrag

AU - Bojesen, Stig Egil

AU - Wu, Xifeng

AU - Albanes, Demetrios

AU - Aldrich, Melinda C.

AU - Tardon, Adonina

AU - Fernandez-Somoano, Ana

AU - Fernandez-Tardon, Guillermo

AU - Le Marchand, Loic

AU - Rennert, Gadi

AU - Chen, Chu

AU - Doherty, Jennifer

AU - Goodman, Gary

AU - Bickeböller, Heike

AU - Wichmann, H. Erich

AU - Risch, Angela

AU - Rosenberger, Albert

AU - Shen, Hongbing

AU - Dai, Juncheng

AU - Field, John K.

AU - Davies, Michael

AU - Woll, Penella

AU - Teare, M. Dawn

AU - Kiemeney, Lambertus A.

AU - van der Heijden, Erik H.F.M.

AU - Yuan, Jian Min

AU - Hong, Yun Chul

AU - Haugen, Aage

AU - Zienolddiny, Shanbeh

AU - Lam, Stephen

AU - Tsao, Ming Sound

AU - Johansson, Mikael

AU - Grankvist, Kjell

AU - Schabath, Matthew B.

AU - Andrew, Angeline

AU - Duell, Eric

AU - Melander, Olle

AU - Brunnström, Hans

AU - Lazarus, Philip

AU - Arnold, Susanne

AU - Slone, Stacey

AU - Byun, Jinyoung

AU - Kamal, Ahsan

AU - Zhu, Dakai

AU - Landi, Maria Teresa

AU - Amos, Christopher I.

AU - Brennan, Paul

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85053845843

UR - https://www.scopus.com/pages/publications/85053845843#tab=citedBy

U2 - 10.1038/s41467-018-05890-2

DO - 10.1038/s41467-018-05890-2

M3 - Article

C2 - 30254314

AN - SCOPUS:85053845843

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3927

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

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