Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.
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Date
2021-03-05ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Cancer Genomics
Cancer Genomics
Language
eng
Date accepted
2020-11-05
License start date
2021-03-05
Citation
PLoS genetics, 2021, 17 (3), pp. e1009254 - ?
Publisher
PUBLIC LIBRARY SCIENCE