Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.
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ICR Authors
Authors
Lesseur, C
Ferreiro-Iglesias, A
McKay, JD
Bossé, Y
Johansson, M
Gaborieau, V
Landi, MT
Christiani, DC
Caporaso, NC
Bojesen, SE
Amos, CI
Shete, S
Liu, G
Rennert, G
Albanes, D
Aldrich, MC
Tardon, A
Chen, C
Triantafillos, L
Field, JK
Teare, MD
Kiemeney, LA
Diergaarde, B
Ferris, RL
Zienolddiny, S
Lam, S
Olshan, AF
Weissler, MC
Lacko, M
Risch, A
Bickeböller, H
Ness, AR
Thomas, S
Le Marchand, L
Schabath, MB
Wünsch-Filho, V
Tajara, EH
Andrew, AS
Clifford, GM
Lazarus, P
Grankvist, K
Johansson, M
Arnold, S
Melander, O
Brunnström, H
Boccia, S
Cadoni, G
Timens, W
Obeidat, M
Xiao, X
Houlston, RS
Hung, RJ
Brennan, P
Ferreiro-Iglesias, A
McKay, JD
Bossé, Y
Johansson, M
Gaborieau, V
Landi, MT
Christiani, DC
Caporaso, NC
Bojesen, SE
Amos, CI
Shete, S
Liu, G
Rennert, G
Albanes, D
Aldrich, MC
Tardon, A
Chen, C
Triantafillos, L
Field, JK
Teare, MD
Kiemeney, LA
Diergaarde, B
Ferris, RL
Zienolddiny, S
Lam, S
Olshan, AF
Weissler, MC
Lacko, M
Risch, A
Bickeböller, H
Ness, AR
Thomas, S
Le Marchand, L
Schabath, MB
Wünsch-Filho, V
Tajara, EH
Andrew, AS
Clifford, GM
Lazarus, P
Grankvist, K
Johansson, M
Arnold, S
Melander, O
Brunnström, H
Boccia, S
Cadoni, G
Timens, W
Obeidat, M
Xiao, X
Houlston, RS
Hung, RJ
Brennan, P
Document Type
Journal Article
Date
2021-03-05
Date Accepted
2020-11-05
Abstract
Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes rel to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.
Citation
PLoS genetics, 2021, 17 (3), pp. e1009254 - ?
Source Title
Publisher
PUBLIC LIBRARY SCIENCE
ISSN
1553-7390
eISSN
1553-7404
Collections
Research Team
Cancer Genomics
Cancer Genomics
Cancer Genomics