Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
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Lu, Yi
Cuellar-Partida, Gabriel
Painter, Jodie N.
Nyholt, Dale R.
Morris, Andrew P.
Fasching, Peter A.
Hein, Alexander
Burghaus, Stefanie
Beckmann, Matthias W.
Lambrechts, Diether
Van Nieuwenhuysen, Els
Vergote, Ignace
Vanderstichele, Adriaan
Doherty, Jennifer Anne
Rossing, Mary Anne
Wicklund, Kristine G.
Chang-Claude, Jenny
Eilber, Ursula
Rudolph, Anja
Wang-Gohrke, Shan
Goodman, Marc T.
Bogdanova, Natalia
Dörk, Thilo
Dürst, Matthias
Hillemanns, Peter
Runnebaum, Ingo B.
Antonenkova, Natalia
Butzow, Ralf
Leminen, Arto
Nevanlinna, Heli
Pelttari, Liisa M.
Edwards, Robert P.
Kelley, Joseph L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Cannioto, Rikki
Høgdall, Estrid
Jensen, Allan
Giles, Graham G.
Bruinsma, Fiona
Kjaer, Susanne K.
Hildebrandt, Michelle A.T.
Liang, Dong
Lu, Karen H.
Wu, Xifeng
Bisogna, Maria
Dao, Fanny
Levine, Douglas A.
Bjorge, Line
Salvesen, Helga B.
Kopperud, Reidun K.
Bischof, Katharina
Aben, Katja K.H.
Kiemeney, Lambertus A.
Massuger, Leon F.A.G.
Brooks-Wilson, Angela
Olson, Sara H.
McGuire, Valerie
Rothstein, Joseph H.
Sieh, Weiva
Whittemore, Alice S.
Cook, Linda S.
Le, Nhu D.
Gilks, C. Blake
Gronwald, Jacek
Jakubowska, Anna
Lubinski, Jan
Gawelko, Jan
Song, Honglin
Tyrer, Jonathan P.
Wentzensen, Nicolas
Brinton, Louise
Trabert, Britton
Lissowska, Jolanta
Mclaughlin, John R.
Narod, Steven A.
Phelan, Catherine
Anton-Culver, Hoda
Ziogas, Argyrios
Eccles, Diana
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Menon, Usha
Ramus, Susan J.
Wu, Anna H.
Dansonka-Mieszkowska, Agnieszka
Kupryjanczyk, Jolanta
Timorek, Agnieszka
Szafron, Lukasz
Cunningham, Julie M.
Fridley, Brooke L.
Winham, Stacey J.
Bandera, Elisa V.
Morgan, Terry K.
Risch, Harvey A.
Goode, Ellen L.
Schildkraut, Joellen M.
Webb, Penelope M.
Pearce, Celeste L.
Berchuck, Andrew
Pharoah, Paul D.P.
Montgomery, Grant W.
Zondervan, Krina T.
Chenevix-Trench, Georgia
MacGregor, Stuart
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1093/hmg/ddv306Metadata
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Lu, Yi, Gabriel Cuellar-Partida, Jodie N. Painter, Dale R. Nyholt, Andrew P. Morris, Peter A. Fasching, Alexander Hein, et al. 2015. “Shared Genetics Underlying Epidemiological Association Between Endometriosis and Ovarian Cancer.” Human Molecular Genetics 24 (20) (July 30): 5955–5964. doi:10.1093/hmg/ddv306.Abstract
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.Citable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:34737215
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