Germline copy number variants and endometrial cancer risk
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Springer
2024
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| _version_ | 1826315223382884352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Stylianou, CE |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-12-09T03:22:02Z |
| format | Journal article |
| id | oxford-uuid:4a24e700-78e7-4520-9c1d-1c700e47c73b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:22:02Z |
| publishDate | 2024 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:4a24e700-78e7-4520-9c1d-1c700e47c73b2024-11-20T20:13:14ZGermline copy number variants and endometrial cancer riskJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4a24e700-78e7-4520-9c1d-1c700e47c73bEnglishJisc Publications RouterSpringer2024Stylianou, CEWiggins, GARLau, VLDennis, JShelling, ANWilson, MSykes, PAmant, FAnnibali, DDe Wispelaere, WEaston, DFFasching, PAGlubb, DMGoode, ELLambrechts, DPharoah, PDPScott, RJTham, ETomlinson, IBolla, MKCouch, FJCzene, KDörk, TDunning, AMKnown 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. |
| spellingShingle | 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 Germline copy number variants and endometrial cancer risk |
| title | Germline copy number variants and endometrial cancer risk |
| title_full | Germline copy number variants and endometrial cancer risk |
| title_fullStr | Germline copy number variants and endometrial cancer risk |
| title_full_unstemmed | Germline copy number variants and endometrial cancer risk |
| title_short | Germline copy number variants and endometrial cancer risk |
| title_sort | germline copy number variants and endometrial cancer risk |
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