Journal Article

DKFZ-2024-02235

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Germline copy number variants and endometrial cancer risk.

Stylianou, C. E. ; Wiggins, G. A. R. ; Lau, V. L. ; Dennis, J. ; Shelling, A. N. ; Wilson, M. ; Sykes, P. ; Amant, F. ; Annibali, D. ; De Wispelaere, W. ; Easton, D. F. ; Fasching, P. A. ; Glubb, D. M. ; Goode, E. L. ; Lambrechts, D. ; Pharoah, P. D. P. ; Scott, R. J. ; Tham, E. ; Tomlinson, I. ; Bolla, M. K. ; Couch, F. J. ; Czene, K. ; Dörk, T. ; Dunning, A. M. ; Fletcher, O. ; García-Closas, M. ; Hoppe, R. ; Investigators, A. (Collaboration Author) ; Jernström, H. ; Kaaks, R.DKFZ* ; Michailidou, K. ; Obi, N. ; Southey, M. C. ; Stone, J. ; Wang, Q. ; Spurdle, A. B. ; O'Mara, T. A. ; Pearson, J. ; Walker, L. C. ; Clarke, C. (Contributor) ; Marsh, D. (Contributor) ; Scott, R. (Contributor) ; Baxter, R. (Contributor) ; Yip, D. (Contributor) ; Carpenter, J. (Contributor) ; Davis, A. (Contributor) ; Pathmanathan, N. (Contributor) ; Simpson, P. (Contributor) ; Dinny Graham, J. (Contributor) ; Sachchithananthan, M. (Contributor)

2024
Springer Heidelberg

This record in other databases:  

Please use a persistent id in citations: doi:10.1007/s00439-024-02707-9

Abstract: 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 and 0.02% of control participants. Together, these data provide evidence that rare copy number variants have a role in endometrial cancer susceptibility and that the proximal 16p11.2 BP4-BP5 region contains 25 candidate risk gene(s) that warrant further analysis to better understand their role in human disease.

Note: Volume 143, pages 1481–1498, (2024)

---

Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---