TY - JOUR
T1 - Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers
AU - Lesseur, Corina
AU - Ferreiro-Iglesias, Aida
AU - McKay, James D.
AU - Bossé, Yohan
AU - Johansson, Mattias
AU - Gaborieau, Valerie
AU - Landi, Maria Teresa
AU - Christiani, David C.
AU - Caporaso, Neil C.
AU - Bojesen, Stig E.
AU - Amos, Christopher I.
AU - Shete, Sanjay
AU - Liu, Geoffrey
AU - Rennert, Gadi
AU - Albanes, Demetrios
AU - Aldrich, Melinda C.
AU - Tardon, Adonina
AU - Chen, Chu
AU - Triantafillos, Liloglou
AU - Field, John K.
AU - Teare, Marion Dawn
AU - Kiemeney, Lambertus A.
AU - Diergaarde, Brenda
AU - Ferris, Robert L.
AU - Zienolddiny, Shanbeh
AU - Lam, Stephen
AU - Olshan, Andrew F.
AU - Weissler, Mark C.
AU - Lacko, Martin
AU - Risch, Angela
AU - Bickeböller, Heike
AU - Ness, Andy R.
AU - Thomas, Steve
AU - Le Marchand, Loic
AU - Schabath, Matthew B.
AU - Wünsch-Filho, Victor
AU - Tajara, Eloiza H.
AU - Andrew, Angeline S.
AU - Clifford, Gary M.
AU - Lazarus, Philip
AU - Grankvist, Kjell
AU - Johansson, Mikael
AU - Arnold, Susanne
AU - Melander, Olle
AU - Brunnström, Hans
AU - Boccia, Stefania
AU - Cadoni, Gabriella
AU - Timens, Wim
AU - Obeidat, Ma'en
AU - Xiao, Xiangjun
AU - Houlston, Richard S.
AU - Hung, Rayjean J.
AU - Brennan, Paul
N1 - Publisher Copyright:
Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2021/3/5
Y1 - 2021/3/5
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85102647478&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1009254
DO - 10.1371/journal.pgen.1009254
M3 - Article
C2 - 33667223
AN - SCOPUS:85102647478
SN - 1553-7390
VL - 17
JO - PLoS Genetics
JF - PLoS Genetics
IS - 3
M1 - e1009254
ER -