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

C. Lesseur, A. Ferreiro-Iglesias, J. D. McKay, Y. Bosse, M. Johansson, V. Gaborieau, M. T. Landi, D. C. Christiani, N. C. Caporaso, S. E. Bojesen, C. I. Amos, S. Shete, G. Liu, G. Rennert, D. Albanes, M. C. Aldrich, A. Tardon, C. Chen, L. Triantafillos, J. K. FieldM. D. Teare, L. A. Kiemeney, B. Diergaarde, R. L. Ferris, S. Zienolddiny, S. Lam, A. F. Olshan, M. C. Weissler, M. Lacko, A. Risch, H. Bickeboller, A. R. Ness, S. Thomas, Marchand L. Le, M. B. Schabath, V. Wunsch-Filho, E. H. Tajara, A. S. Andrew, G. M. Clifford, P. Lazarus, K. Grankvist, M. Johansson, S. Arnold, O. Melander, H. Brunnstrom, Stefania Boccia, Gabriella Cadoni, W. Timens, M. Obeidat, X. Xiao, R. S. Houlston, R. J. Hung*, P. Brennan*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo

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 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.
Lingua originaleInglese
pagine (da-a)e1009254-e1009254
RivistaPLoS Genetics
Volume17
Numero di pubblicazione3
DOI
Stato di pubblicazionePubblicato - 2021

All Science Journal Classification (ASJC) codes

  • Ecologia, Evoluzione, Comportamento e Sistematica
  • Biologia Molecolare
  • Genetica
  • Genetica (clinica)
  • Ricerca sul Cancro

Keywords

  • head and neck

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