| Literature DB >> 27075448 |
Gabriel Cuellar-Partida1,2, Yi Lu3, Suzanne C Dixon4,5, Peter A Fasching6,7, Alexander Hein7, Stefanie Burghaus7, Matthias W Beckmann7, Diether Lambrechts8,9, Els Van Nieuwenhuysen10, Ignace Vergote10, Adriaan Vanderstichele10, Jennifer Anne Doherty11, Mary Anne Rossing12,13, Jenny Chang-Claude14,15, Anja Rudolph14, Shan Wang-Gohrke16, Marc T Goodman17,18, Natalia Bogdanova19, Thilo Dörk20, Matthias Dürst21, Peter Hillemanns22, Ingo B Runnebaum21, Natalia Antonenkova23, Ralf Butzow24, Arto Leminen25, Heli Nevanlinna25, Liisa M Pelttari25, Robert P Edwards26,27, Joseph L Kelley26, Francesmary Modugno26,27,28, Kirsten B Moysich29, Roberta B Ness30, Rikki Cannioto29, Estrid Høgdall31,32, Claus Høgdall33, Allan Jensen31, Graham G Giles34,35,36, Fiona Bruinsma36, Susanne K Kjaer31,33, Michelle A T Hildebrandt37, Dong Liang38, Karen H Lu39, Xifeng Wu37, Maria Bisogna40, Fanny Dao40, Douglas A Levine40, Daniel W Cramer41, Kathryn L Terry41,42, Shelley S Tworoger42,43, Meir Stampfer42,43, Stacey Missmer41,42,43, Line Bjorge44,45, Helga B Salvesen44,45, Reidun K Kopperud44,45, Katharina Bischof44,45, Katja K H Aben46,47, Lambertus A Kiemeney46, Leon F A G Massuger48, Angela Brooks-Wilson49,50, Sara H Olson51, Valerie McGuire52, Joseph H Rothstein52, Weiva Sieh52, Alice S Whittemore52, Linda S Cook53, Nhu D Le54, C Blake Gilks55, Jacek Gronwald56, Anna Jakubowska56, Jan Lubiński56, Tomasz Kluz57, Honglin Song58, Jonathan P Tyrer58, Nicolas Wentzensen59, Louise Brinton59, Britton Trabert59, Jolanta Lissowska60, John R McLaughlin61, Steven A Narod62, Catherine Phelan63, Hoda Anton-Culver64,65, Argyrios Ziogas64, Diana Eccles66, Ian Campbell67, Simon A Gayther68, Aleksandra Gentry-Maharaj69, Usha Menon69, Susan J Ramus68, Anna H Wu68, Agnieszka Dansonka-Mieszkowska70, Jolanta Kupryjanczyk70, Agnieszka Timorek71, Lukasz Szafron70, Julie M Cunningham72, Brooke L Fridley73, Stacey J Winham74, Elisa V Bandera75, Elizabeth M Poole43, Terry K Morgan76,77, Ellen L Goode78, Joellen M Schildkraut79, Celeste L Pearce68,80, Andrew Berchuck81, Paul D P Pharoah82,58, Penelope M Webb4,5, Georgia Chenevix-Trench83, Harvey A Risch84, Stuart MacGregor85.
Abstract
Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 ± 1.1 %), endometrioid ([Formula: see text] = 3.2 ± 1.6 %), clear cell ([Formula: see text] = 6.7 ± 3.3 %) and all EOC ([Formula: see text] = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.Entities:
Mesh：
Year: 2016 PMID： 27075448 PMCID： PMC4976079 DOI： 10.1007/s00439-016-1663-9
Source DB: PubMed Journal: Hum Genet ISSN： 0340-6717 Impact factor: 5.881