000294406 001__ 294406 000294406 005__ 20241120135326.0 000294406 0247_ $$2doi$$a10.1007/s00439-024-02707-9 000294406 0247_ $$2pmid$$apmid:39495297 000294406 0247_ $$2ISSN$$a0018-7348 000294406 0247_ $$2ISSN$$a0340-6717 000294406 0247_ $$2ISSN$$a1432-1203 000294406 037__ $$aDKFZ-2024-02235 000294406 041__ $$aEnglish 000294406 082__ $$a610 000294406 1001_ $$aStylianou, Cassie E$$b0 000294406 245__ $$aGermline copy number variants and endometrial cancer risk. 000294406 260__ $$aHeidelberg$$bSpringer$$c2024 000294406 3367_ $$2DRIVER$$aarticle 000294406 3367_ $$2DataCite$$aOutput Types/Journal article 000294406 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1732107172_28810 000294406 3367_ $$2BibTeX$$aARTICLE 000294406 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000294406 3367_ $$00$$2EndNote$$aJournal Article 000294406 500__ $$aVolume 143, pages 1481–1498, (2024) 000294406 520__ $$aKnown 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. 000294406 536__ $$0G:(DE-HGF)POF4-313$$a313 - Krebsrisikofaktoren und Prävention (POF4-313)$$cPOF4-313$$fPOF IV$$x0 000294406 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000294406 7001_ $$aWiggins, George A R$$b1 000294406 7001_ $$aLau, Vanessa L$$b2 000294406 7001_ $$aDennis, Joe$$b3 000294406 7001_ $$aShelling, Andrew N$$b4 000294406 7001_ $$aWilson, Michelle$$b5 000294406 7001_ $$aSykes, Peter$$b6 000294406 7001_ $$aAmant, Frederic$$b7 000294406 7001_ $$aAnnibali, Daniela$$b8 000294406 7001_ $$aDe Wispelaere, Wout$$b9 000294406 7001_ $$aEaston, Douglas F$$b10 000294406 7001_ $$aFasching, Peter A$$b11 000294406 7001_ $$aGlubb, Dylan M$$b12 000294406 7001_ $$aGoode, Ellen L$$b13 000294406 7001_ $$aLambrechts, Diether$$b14 000294406 7001_ $$aPharoah, Paul D P$$b15 000294406 7001_ $$aScott, Rodney J$$b16 000294406 7001_ $$aTham, Emma$$b17 000294406 7001_ $$aTomlinson, Ian$$b18 000294406 7001_ $$aBolla, Manjeet K$$b19 000294406 7001_ $$aCouch, Fergus J$$b20 000294406 7001_ $$aCzene, Kamila$$b21 000294406 7001_ $$aDörk, Thilo$$b22 000294406 7001_ $$aDunning, Alison M$$b23 000294406 7001_ $$aFletcher, Olivia$$b24 000294406 7001_ $$aGarcía-Closas, Montserrat$$b25 000294406 7001_ $$aHoppe, Reiner$$b26 000294406 7001_ $$aInvestigators, ABCTB$$b27$$eCollaboration Author 000294406 7001_ $$aJernström, Helena$$b28 000294406 7001_ $$0P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aKaaks, Rudolf$$b29$$udkfz 000294406 7001_ $$aMichailidou, Kyriaki$$b30 000294406 7001_ $$aObi, Nadia$$b31 000294406 7001_ $$aSouthey, Melissa C$$b32 000294406 7001_ $$aStone, Jennifer$$b33 000294406 7001_ $$aWang, Qin$$b34 000294406 7001_ $$aSpurdle, Amanda B$$b35 000294406 7001_ $$aO'Mara, Tracy A$$b36 000294406 7001_ $$aPearson, John$$b37 000294406 7001_ $$aWalker, Logan C$$b38 000294406 7001_ $$aClarke, Christine$$b39$$eContributor 000294406 7001_ $$aMarsh, Deborah$$b40$$eContributor 000294406 7001_ $$aScott, Rodney$$b41$$eContributor 000294406 7001_ $$aBaxter, Robert$$b42$$eContributor 000294406 7001_ $$aYip, Desmond$$b43$$eContributor 000294406 7001_ $$aCarpenter, Jane$$b44$$eContributor 000294406 7001_ $$aDavis, Alison$$b45$$eContributor 000294406 7001_ $$aPathmanathan, Nirmala$$b46$$eContributor 000294406 7001_ $$aSimpson, Peter$$b47$$eContributor 000294406 7001_ $$aDinny Graham, J.$$b48$$eContributor 000294406 7001_ $$aSachchithananthan, Mythily$$b49$$eContributor 000294406 773__ $$0PERI:(DE-600)1459188-1$$a10.1007/s00439-024-02707-9$$p1481–1498$$tHuman genetics$$v143$$x0018-7348$$y2024 000294406 909CO $$ooai:inrepo02.dkfz.de:294406$$pVDB 000294406 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4b2dc91c9d1ac33a1c0e0777d0c1697a$$aDeutsches Krebsforschungszentrum$$b29$$kDKFZ 000294406 9131_ $$0G:(DE-HGF)POF4-313$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vKrebsrisikofaktoren und Prävention$$x0 000294406 9141_ $$y2024 000294406 915__ $$0StatID:(DE-HGF)3002$$2StatID$$aDEAL Springer$$d2023-08-19$$wger 000294406 915__ $$0StatID:(DE-HGF)3002$$2StatID$$aDEAL Springer$$d2023-08-19$$wger 000294406 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bHUM GENET : 2022$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-08-19 000294406 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bHUM GENET : 2022$$d2023-08-19 000294406 9201_ $$0I:(DE-He78)C020-20160331$$kC020$$lC020 Epidemiologie von Krebs$$x0 000294406 980__ $$ajournal 000294406 980__ $$aVDB 000294406 980__ $$aI:(DE-He78)C020-20160331 000294406 980__ $$aUNRESTRICTED