Lesseur, Corina, Ferreiro-Iglesias, Aida, McKay, James D, Bosse, Yohan, Johansson, Mattias, Gaborieau, Valerie, Landi, Maria Teresa, Christiani, David C, Caporaso, Neil C, Bojesen, Stig E et al (show 43 more authors)
(2021)
Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.
PLOS GENETICS, 17 (3).
e1009254-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Carcinoma, Squamous Cell, Digestive System Neoplasms, Genetic Predisposition to Disease, Odds Ratio, Signal Transduction, Genotype, Alleles, Genome-Wide Association Study, Genetic Loci, Biomarkers, Tumor |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 12 Mar 2021 11:08 |
| Last Modified: | 18 Jan 2023 22:56 |
| DOI: | 10.1371/journal.pgen.1009254 |
| Open Access URL: | https://journals.plos.org/plosgenetics/article?id=... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3117096 |
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