Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

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 SqC...

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Detalles Bibliográficos
Autores principales: Lesseur, Corina, Ferreiro-Iglesias, Aida, McKay, James D., Bossé, Yohan, Johansson, Mattias, Gaborieau, Valerie, Landi, Maria Teresa, Christiani, David C., Caporaso, Neil C., Bojesen, Stig E., Amos, Christopher I., Shete, Sanjay, Liu, Geoffrey, Rennert, Gadi, Albanes, Demetrius, Aldrich, Melinda C., Tardon, Adonina, Chen, Chu, Triantafillos, Liloglou, Field, John K., Teare, Marion Dawn, Kiemeney, Lambertus A., Diergaarde, Brenda, Ferris, Robert L., Zienolddiny, Shanbeh, Lam, Stephen, Olshan, Andrew F., Weissler, Mark C., Lacko, Martin, Risch, Angela, Bickeböller, Heike, Ness, Andy R., Thomas, Steve, Le Marchand, Loic, Schabath, Matthew B., Wünsch-Filho, Victor, Tajara, Eloiza H., Andrew, Angeline S., Clifford, Gary M., Lazarus, Philip, Grankvist, Kjell, Johansson, Mikael, Arnold, Susanne, Melander, Olle, Brunnström, Hans, Boccia, Stefania, Cadoni, Gabriella, Timens, Wim, Obeidat, Ma’en, Xiao, Xiangjun, Houlston, Richard S., Hung, Rayjean J., Brennan, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968735/
https://www.ncbi.nlm.nih.gov/pubmed/33667223
http://dx.doi.org/10.1371/journal.pgen.1009254
Descripción
Sumario: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 (P(meta)<5x10(-8)) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (P(meta)<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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