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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 3927 |
Tidsskrift | Nature Communications |
Vol/bind | 9 |
Antal sider | 12 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 2018 |
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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity. / 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.
I: Nature Communications, Bind 9, 3927, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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
Y1 - 2018
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.
KW - Asian Continental Ancestry Group/genetics
KW - Chromosome Mapping
KW - European Continental Ancestry Group/genetics
KW - Female
KW - Gene Frequency
KW - Genetic Predisposition to Disease/ethnology
KW - Genotype
KW - HLA Antigens/genetics
KW - Humans
KW - Lung Neoplasms/ethnology
KW - Major Histocompatibility Complex/genetics
KW - Male
KW - Middle Aged
KW - Peptides/genetics
KW - Polymorphism, Single Nucleotide
U2 - 10.1038/s41467-018-05890-2
DO - 10.1038/s41467-018-05890-2
M3 - Journal article
C2 - 30254314
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3927
ER -