Known risk loci for endometrial cancer explain approximately one third of familial endometrial cancer. However, the association of germline copy number variants (CNVs) with endometrial cancer risk remains relatively unknown. We conducted a genome-wide analysis of rare CNVs overlapping gene regions in 4115 endometrial cancer cases and 17,818 controls to identify functionally relevant variants associated with disease. We identified a 1.22-fold greater number of CNVs in DNA samples from cases compared to DNA samples from controls (p?=?4.4?×?10-63). Under three models of putative CNV impact (deletion, duplication, and loss of function), genome-wide association studies identified 141 candidate gene loci associated (p?<?0.01) with endometrial cancer risk. Pathway analysis of the candidate loci revealed an enrichment of genes involved in the 16p11.2 proximal deletion syndrome, driven by a large recurrent deletion (chr16:29,595,483-30,159,693) identified in 0.15% of endometrial cancer cases an...
| Authors | Stylianou, CE; Wiggins, GAR; Lau, VL; Dennis, J; Shelling, AN; Wilson, M; Sykes, P; Amant, F; Annibali, D; De Wispelaere, W; Easton, DF; Fasching, PA; Glubb, DM; Goode, EL; Lambrechts, D; Pharoah, PDP; Scott, RJ; Tham, E; Tomlinson, I; Bolla, MK; Couch, FJ; Czene, K; Dörk, T; Dunning, AM; Fletcher, O; García-Closas, M; Hoppe, R; ABCTB Investigators; Jernström, H; Kaaks, R; Michailidou, K; Obi, N; Southey, MC; Stone, J; Wang, Q; Spurdle, AB; O'Mara, TA; Pearson, J; Walker, LC |
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| Journal | HUMAN GENETICS |
| Pages | 1481-1498 |
| Volume | 143 |
| Date | 4/12/2024 |
| Grant ID | APP177524 | National Health and Medical Research Council; R01 CA128931 | NCI NIH HHS [CA] (United States); R01 CA176785 | NCI NIH HHS [CA] (United States); UM1 CA164920 | NCI NIH HHS [CA] (United States); APP1111246 | National Health and Medical Research Council; R01 CA097396 | NCI NIH HHS [CA] (United States); R01 CA058598 | NCI NIH HHS [CA] (United States); P50 CA116201 | NCI NIH HHS [CA] (United States); R01 CA149429 | NCI NIH HHS [CA] (United States); R01 CA192393 | NCI NIH HHS [CA] (United States); R01 CA116167 | NCI NIH HHS [CA] (United States); R01 CA177150 | NCI NIH HHS [CA] (United States); #19/460 | Health Research Council of New Zealand; R01 CA122443 | NCI NIH HHS [CA] (United States); P30 CA015083 | NCI NIH HHS [CA] (United States); R35 CA253187 | NCI NIH HHS [CA] (United States); U19 CA148112 | NCI NIH HHS [CA] (United States); U19 CA148065 | NCI NIH HHS [CA] (United States); Wellcome Trust [WT_] (United Kingdom); R01 CA140286 | NCI NIH HHS [CA] (United States); P50 CA136393 | NCI NIH HHS [CA] (United States) |
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| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1007/s00439-024-02707-9 |