Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers. Other Scholarly Work

Lesseur, Corina, Ferreiro-Iglesias, Aida, McKay, James D et al. (2021). Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers. . 17(3), e1009254. 10.1371/journal.pgen.1009254

cited authors

  • 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

fiu authors

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.

publication date

  • March 5, 2021

keywords

  • Alleles
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell
  • Digestive System Neoplasms
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Odds Ratio
  • Signal Transduction

Digital Object Identifier (DOI)

Medium

  • Electronic-eCollection

start page

  • e1009254

volume

  • 17

issue

  • 3