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

2.50
Hdl Handle:
http://hdl.handle.net/10146/618226
Title:
Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity.
Authors:
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
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.
Affiliation:
Nofer Institute of Occupational Medicine
Citation:
Nat Commun 2018, 9 (1):3927
Journal:
Nature Communications
Issue Date:
25-Sep-2018
URI:
http://hdl.handle.net/10146/618226
DOI:
10.1038/s41467-018-05890-2
PubMed ID:
30254314
Additional Links:
https://www.nature.com/articles/s41467-018-05890-2
Type:
Article
Language:
en
ISSN:
2041-1723
Sponsors:
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.
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Full metadata record

DC FieldValue Language
dc.contributor.authorFerreiro-Iglesias, Aidaen
dc.contributor.authorLesseur, Corinaen
dc.contributor.authorMcKay, Jamesen
dc.contributor.authorHung, Rayjean Jen
dc.contributor.authorHan, Younghunen
dc.contributor.authorZong, Xuchenen
dc.contributor.authorChristiani, Daviden
dc.contributor.authorJohansson, Mattiasen
dc.contributor.authorXiao, Xiangjunen
dc.contributor.authorLi, Yafangen
dc.contributor.authorQian, David Cen
dc.contributor.authorJi, Xuemeien
dc.contributor.authorLiu, Geoffreyen
dc.contributor.authorCaporaso, Neilen
dc.contributor.authorScelo, Ghislaineen
dc.contributor.authorZaridze, Daviden
dc.contributor.authorMukeriya, Anushen
dc.contributor.authorKontic, Milicaen
dc.contributor.authorOgnjanovic, Simonaen
dc.contributor.authorLissowska, Jolantaen
dc.contributor.authorSzołkowska, Małgorzataen
dc.contributor.authorSwiatkowska, Beataen
dc.contributor.authorJanout, Vladimiren
dc.contributor.authorHolcatova, Ivanaen
dc.contributor.authorBolca, Ciprianen
dc.contributor.authorSavic, Milanen
dc.contributor.authorOgnjanovic, Miodragen
dc.contributor.authorBojesen, Stig Egilen
dc.contributor.authorWu, Xifengen
dc.contributor.authorAlbanes, Demetriosen
dc.contributor.authorAldrich, Melinda Cen
dc.contributor.authorTardon, Adoninaen
dc.contributor.authorFernandez-Somoano, Anaen
dc.contributor.authorFernandez-Tardon, Guillermoen
dc.contributor.authorLe Marchand, Loicen
dc.contributor.authorRennert, Gadien
dc.contributor.authorChen, Chuen
dc.contributor.authorDoherty, Jenniferen
dc.contributor.authorGoodman, Garyen
dc.contributor.authorBickeböller, Heikeen
dc.contributor.authorWichmann, H-Erichen
dc.contributor.authorRisch, Angelaen
dc.contributor.authorRosenberger, Alberten
dc.contributor.authorShen, Hongbingen
dc.contributor.authorDai, Junchengen
dc.contributor.authorField, John Ken
dc.contributor.authorDavies, Michaelen
dc.contributor.authorWoll, Penellaen
dc.contributor.authorTeare, M Dawnen
dc.contributor.authorKiemeney, Lambertus Aen
dc.contributor.authorvan der Heijden, Erik H F Men
dc.contributor.authorYuan, Jian-Minen
dc.contributor.authorHong, Yun-Chulen
dc.contributor.authorHaugen, Aageen
dc.contributor.authorZienolddiny, Shanbehen
dc.contributor.authorLam, Stephenen
dc.contributor.authorTsao, Ming-Sounden
dc.contributor.authorJohansson, Mikaelen
dc.contributor.authorGrankvist, Kjellen
dc.contributor.authorSchabath, Matthew Ben
dc.contributor.authorAndrew, Angelineen
dc.contributor.authorDuell, Ericen
dc.contributor.authorMelander, Olleen
dc.contributor.authorBrunnström, Hansen
dc.contributor.authorLazarus, Philipen
dc.contributor.authorArnold, Susanneen
dc.contributor.authorSlone, Staceyen
dc.contributor.authorByun, Jinyoungen
dc.contributor.authorKamal, Ahsanen
dc.contributor.authorZhu, Dakaien
dc.contributor.authorLandi, Maria Teresaen
dc.contributor.authorAmos, Christopher Ien
dc.contributor.authorBrennan, Paulen
dc.date.accessioned2018-12-03T10:41:05Z-
dc.date.available2018-12-03T10:41:05Z-
dc.date.issued2018-09-25-
dc.identifier.citationNat Commun 2018, 9 (1):3927en
dc.identifier.issn2041-1723-
dc.identifier.pmid30254314-
dc.identifier.doi10.1038/s41467-018-05890-2-
dc.identifier.urihttp://hdl.handle.net/10146/618226-
dc.description.abstractLung 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.en
dc.description.sponsorshipTransdisciplinary 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.en
dc.language.isoenen
dc.relation.urlhttps://www.nature.com/articles/s41467-018-05890-2en
dc.rightsArchived with thanks to Nature communicationsen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectlung canceren
dc.titleFine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicineen
dc.identifier.journalNature Communicationsen

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