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33667223
Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers.

PLoS Genet, 2021/03;17(3):e1009254.

Lesseur C[1, 2], Ferreiro-Iglesias A[1], McKay JD[3], Bossé Y[4], Johansson M[1], Gaborieau V[1], Landi MT[5], Christiani DC[6], Caporaso NC[5], Bojesen SE[7], Amos CI[8], Shete S[9], Liu G[10], Rennert G[11], Albanes D[5], Aldrich MC[12], Tardon A[13], Chen C[14], Triantafillos L[15], Field JK[15], Teare MD[16], Kiemeney LA[17], Diergaarde B[18, 19, 20], Ferris RL[20], Zienolddiny S[21], Lam S[22], Olshan AF[23], Weissler MC[24], Lacko M[25], Risch A[26, 27, 28], Bickeböller H[29], Ness AR[30, 31], Thomas S[31], Le Marchand L[32], Schabath MB[33], Wünsch-Filho V[34], Tajara EH[35], Andrew AS[36], Clifford GM[37], Lazarus P[38], Grankvist K[39], Johansson M[40], Arnold S[41], Melander O[42, 43], Brunnström H[44], Boccia S[45, 46], Cadoni G[47, 48], Timens W[49, 50], Obeidat M[51], Xiao X[8], Houlston RS[52], Hung RJ[53], Brennan P[1]

Affiliations

PMID: 33667223DOI: 10.1371/journal.pgen.1009254

Impact factor: 6.02

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.
MeSH terms
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
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