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Region Hovedstaden - en del af Københavns Universitetshospital
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Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers

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  • Dylan M Glubb
  • Deborah J Thompson
  • Katja Kh Aben
  • Ahmad Alsulimani
  • Frédéric Amant
  • Daniela Annibali
  • John Attia
  • Aurelio Barricarte
  • Matthias W Beckmann
  • Andrew Berchuck
  • Marina Bermisheva
  • Marcus Q Bernardini
  • Katharina Bischof
  • Line Bjørge
  • Clara Bodelon
  • Alison H Brand
  • James D Brenton
  • Louise A Brinton
  • Fiona Bruinsma
  • Daniel D Buchanan
  • Stefanie Burghaus
  • Ralf Bützow
  • Hui Cai
  • Michael E Carney
  • Stephen J Chanock
  • Chu Chen
  • Xiaoqing Chen
  • Zhihua Chen
  • Linda S Cook
  • Julie M Cunningham
  • Immaculata De Vivo
  • Anna DeFazio
  • Jennifer A Doherty
  • Thilo Dork
  • Andreas du Bois
  • Alison M Dunning
  • Matthias Durst
  • Todd Edwards
  • Robert P Edwards
  • Arif B Ekici
  • Ailith Ewing
  • Peter A Fasching
  • Sarah Ferguson
  • James M Flanagan
  • Florentia Fostira
  • George Fountzilas
  • Christine M Friedenreich
  • Bo Gao
  • Mia M Gaudet
  • Jan Gawełko
  • Aleksandra Gentry-Maharaj
  • Graham G Giles
  • Rosalind Glasspool
  • Marc T Goodman
  • Jacek Gronwald
  • Holly R Harris
  • Philipp Harter
  • Alexander Hein
  • Florian Heitz
  • Michelle A T Hildebrandt
  • Peter Hillemanns
  • Estrid Høgdall
  • Claus K Høgdall
  • Elizabeth G Holliday
  • David G Huntsman
  • Tomasz Huzarski
  • Anna Jakubowska
  • Michael E Jones
  • Beth Y Karlan
  • Anthony Karnezis
  • Joseph L Kelley
  • Elza Khusnutdinova
  • Jeffrey L Killeen
  • Susanne K Kjaer
  • Rüdiger Klapdor
  • Martin Köbel
  • Bozena Konopka
  • Irene Konstantopoulou
  • Reidun K Kopperud
  • Madhuri Koti
  • Peter Kraft
  • Jolanta Kupryjanczyk
  • Diether Lambrechts
  • Melissa C Larson
  • Loic Le Marchand
  • Shashikant Lele
  • Jenny Lester
  • Andrew J Li
  • Dong Liang
  • Clemens Liebrich
  • Loren Lipworth
  • Jolanta Lissowska
  • Lingeng Lu
  • Karen H Lu
  • Alessandra Macciotta
  • Amalia Mattiello
  • Taymaa May
  • Jessica N McAlpine
  • Valerie McGuire
  • Iain A McNeish
  • Usha Menon
  • Francesmary Modugno
  • Kirsten B Moysich
  • Heli Nevanlinna
  • Kunle Odunsi
  • Håkan Olsson
  • Sandra Orsulic
  • Ana Osorio
  • Domenico Palli
  • Tjoung-Won Park-Simon
  • Celeste L Pearce
  • Tanja Pejovic
  • Jennifer B Permuth
  • Agnieszka Podgorska
  • Susan J Ramus
  • Timothy R Rebbeck
  • Marjorie J Riggan
  • Harvey A Risch
  • Joseph H Rothstein
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  • Liv Cecilie Vestrheim Thomsen
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  • Constance Turman
  • Adriaan Vanderstichele
  • Digna Velez Edwards
  • Ignace Vergote
  • Robert A Vierkant
  • Zhaoming Wang
  • Shan Wang-Gohrke
  • Penelope M Webb
  • Emily White
  • Alice S Whittemore
  • Stacey J Winham
  • Xifeng Wu
  • Anna H Wu
  • Drakoulis Yannoukakos
  • Amanda B Spurdle
  • Tracy A O'Mara
Vis graf over relationer

BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( r G = 0.43, P = 2.66 × 10 -5). We found seven loci associated with risk for both cancers ( P Bonferroni < 2.4 × 10 -9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( P < 5 × 10 -7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.

OriginalsprogEngelsk
TidsskriftCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Vol/bind30
Udgave nummer1
Sider (fra-til)217-228
Antal sider12
ISSN1055-9965
DOI
StatusUdgivet - jan. 2021

ID: 61425002