Germline copy number variants and endometrial cancer risk.
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
- Publisher:
- Springer Nature
- Publication Type:
- Journal Article
- Citation:
- Hum Genet, 2024, 143, (12), pp. 1481-1498
- Issue Date:
- 2024-12
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Stylianou, CE | |
dc.contributor.author | Wiggins, GAR | |
dc.contributor.author | Lau, VL | |
dc.contributor.author | Dennis, J | |
dc.contributor.author | Shelling, AN | |
dc.contributor.author | Wilson, M | |
dc.contributor.author | Sykes, P | |
dc.contributor.author | Amant, F | |
dc.contributor.author | Annibali, D | |
dc.contributor.author | De Wispelaere, W | |
dc.contributor.author | Easton, DF | |
dc.contributor.author | Fasching, PA | |
dc.contributor.author | Glubb, DM | |
dc.contributor.author | Goode, EL | |
dc.contributor.author | Lambrechts, D | |
dc.contributor.author | Pharoah, PDP | |
dc.contributor.author | Scott, RJ | |
dc.contributor.author | Tham, E | |
dc.contributor.author | Tomlinson, I | |
dc.contributor.author | Bolla, MK | |
dc.contributor.author | Couch, FJ | |
dc.contributor.author | Czene, K | |
dc.contributor.author | Dörk, T | |
dc.contributor.author | Dunning, AM | |
dc.contributor.author | Fletcher, O | |
dc.contributor.author | García-Closas, M | |
dc.contributor.author | Hoppe, R | |
dc.contributor.author | ABCTB Investigators, | |
dc.contributor.author | Jernström, H | |
dc.contributor.author | Kaaks, R | |
dc.contributor.author | Michailidou, K | |
dc.contributor.author | Obi, N | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Stone, J | |
dc.contributor.author | Wang, Q | |
dc.contributor.author | Spurdle, AB | |
dc.contributor.author | O'Mara, TA | |
dc.contributor.author | Pearson, J | |
dc.contributor.author | Walker, LC | |
dc.date.accessioned | 2025-01-06T00:27:06Z | |
dc.date.available | 2024-09-30 | |
dc.date.available | 2025-01-06T00:27:06Z | |
dc.date.issued | 2024-12 | |
dc.identifier.citation | Hum Genet, 2024, 143, (12), pp. 1481-1498 | |
dc.identifier.issn | 0340-6717 | |
dc.identifier.issn | 1432-1203 | |
dc.identifier.uri | http://hdl.handle.net/10453/182981 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.publisher | Springer Nature | |
dc.relation.ispartof | Hum Genet | |
dc.relation.isbasedon | 10.1007/s00439-024-02707-9 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 0604 Genetics, 1104 Complementary and Alternative Medicine, 1114 Paediatrics and Reproductive Medicine | |
dc.subject.classification | Genetics & Heredity | |
dc.subject.classification | 3105 Genetics | |
dc.subject.classification | 3215 Reproductive medicine | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Female | |
dc.subject.mesh | Endometrial Neoplasms | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | Genome-Wide Association Study | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Case-Control Studies | |
dc.subject.mesh | Germ-Line Mutation | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Chromosomes, Human, Pair 16 | |
dc.subject.mesh | Risk Factors | |
dc.subject.mesh | Chromosomes, Human, Pair 16 | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Endometrial Neoplasms | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Risk Factors | |
dc.subject.mesh | Case-Control Studies | |
dc.subject.mesh | Germ-Line Mutation | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Female | |
dc.subject.mesh | Genome-Wide Association Study | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Female | |
dc.subject.mesh | Endometrial Neoplasms | |
dc.subject.mesh | DNA Copy Number Variations | |
dc.subject.mesh | Genome-Wide Association Study | |
dc.subject.mesh | Genetic Predisposition to Disease | |
dc.subject.mesh | Case-Control Studies | |
dc.subject.mesh | Germ-Line Mutation | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Polymorphism, Single Nucleotide | |
dc.subject.mesh | Chromosomes, Human, Pair 16 | |
dc.subject.mesh | Risk Factors | |
dc.title | Germline copy number variants and endometrial cancer risk. | |
dc.type | Journal Article | |
utslib.citation.volume | 143 | |
utslib.location.activity | Germany | |
utslib.for | 0604 Genetics | |
utslib.for | 1104 Complementary and Alternative Medicine | |
utslib.for | 1114 Paediatrics and Reproductive Medicine | |
pubs.organisational-group | University of Technology Sydney | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | University of Technology Sydney/UTS Groups | |
pubs.organisational-group | University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT) | |
utslib.copyright.status | open_access | * |
dc.rights.license | This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ | |
dc.date.updated | 2025-01-06T00:27:03Z | |
pubs.issue | 12 | |
pubs.publication-status | Published | |
pubs.volume | 143 | |
utslib.citation.issue | 12 |
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.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph