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

Vit. artikkel

Publisert

  • 2021

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.

Lesseur, Corina; Ferreiro-Iglesias, Aida; McKay, James D.; Bossé, Yohan; Johansson, Mattias; Gaborieau, Valerie; Landi, Maria Teresa; Christiani, David C.; Caporaso, Neil E.; Bojesen, Stig E.; Amos, Christopher I.; Shete, Sanjay S.; 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, Loïc; Schabath, Matthew B.; Wunsch-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
PLoS Genetics Public Library of Science (PLoS), PLoS Genetics 17(3)
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