| Literature DB >> 26231222 |
Yi Lu1, Gabriel Cuellar-Partida1, Jodie N Painter2, Dale R Nyholt3, Andrew P Morris4, Peter A Fasching5, Alexander Hein6, Stefanie Burghaus6, Matthias W Beckmann6, Diether Lambrechts7, Els Van Nieuwenhuysen8, Ignace Vergote8, Adriaan Vanderstichele8, Jennifer Anne Doherty9, Mary Anne Rossing10, Kristine G Wicklund11, Jenny Chang-Claude12, Ursula Eilber12, Anja Rudolph12, Shan Wang-Gohrke13, Marc T Goodman14, Natalia Bogdanova15, Thilo Dörk16, Matthias Dürst17, Peter Hillemanns18, Ingo B Runnebaum17, Natalia Antonenkova19, Ralf Butzow20, Arto Leminen21, Heli Nevanlinna21, Liisa M Pelttari21, Robert P Edwards22, Joseph L Kelley23, Francesmary Modugno24, Kirsten B Moysich25, Roberta B Ness26, Rikki Cannioto25, Estrid Høgdall27, Allan Jensen28, Graham G Giles29, Fiona Bruinsma30, Susanne K Kjaer31, Michelle A T Hildebrandt32, Dong Liang33, Karen H Lu34, Xifeng Wu32, Maria Bisogna35, Fanny Dao35, Douglas A Levine35, Daniel W Cramer36, Kathryn L Terry37, Shelley S Tworoger38, Stacey Missmer39, Line Bjorge40, Helga B Salvesen40, Reidun K Kopperud40, Katharina Bischof40, Katja K H Aben41, Lambertus A Kiemeney42, Leon F A G Massuger43, Angela Brooks-Wilson44, Sara H Olson45, Valerie McGuire46, Joseph H Rothstein46, Weiva Sieh46, Alice S Whittemore46, Linda S Cook47, Nhu D Le48, C Blake Gilks49, Jacek Gronwald50, Anna Jakubowska50, Jan Lubiński50, Jan Gawełko51, Honglin Song52, Jonathan P Tyrer52, Nicolas Wentzensen53, Louise Brinton53, Britton Trabert53, Jolanta Lissowska54, John R Mclaughlin55, Steven A Narod56, Catherine Phelan57, Hoda Anton-Culver58, Argyrios Ziogas32, Diana Eccles59, Simon A Gayther60, Aleksandra Gentry-Maharaj61, Usha Menon61, Susan J Ramus60, Anna H Wu60, Agnieszka Dansonka-Mieszkowska62, Jolanta Kupryjanczyk62, Agnieszka Timorek63, Lukasz Szafron62, Julie M Cunningham64, Brooke L Fridley65, Stacey J Winham66, Elisa V Bandera67, Elizabeth M Poole38, Terry K Morgan68, Harvey A Risch69, Ellen L Goode70, Joellen M Schildkraut71, Penelope M Webb72, Celeste L Pearce73, Andrew Berchuck74, Paul D P Pharoah75, Grant W Montgomery76, Krina T Zondervan77, Georgia Chenevix-Trench78, Stuart MacGregor79.
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.Entities:
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Year: 2015 PMID： 26231222 PMCID： PMC4581608 DOI： 10.1093/hmg/ddv306
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150