Skip to Content
Discovering the causes of cancer and the means of prevention

Publications Search - Abstract View

Title: Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.
Authors: Cuellar-Partida G,  Lu Y,  Dixon SC,  Australian Ovarian Cancer Study,  Fasching PA,  Hein A,  Burghaus S,  Beckmann MW,  Lambrechts D,  Van Nieuwenhuysen E,  Vergote I,  Vanderstichele A,  Doherty JA,  Rossing MA,  Chang-Claude J,  Rudolph A,  Wang-Gohrke S,  Goodman MT,  Bogdanova N,  Dörk T,  Dürst M,  Hillemanns P,  Runnebaum IB,  Antonenkova N,  Butzow R,  Leminen A,  Nevanlinna H,  Pelttari LM,  Edwards RP,  Kelley JL,  Modugno F,  Moysich KB,  Ness RB,  Cannioto R,  Høgdall E,  Høgdall C,  Jensen A,  Giles GG,  Bruinsma F,  Kjaer SK,  Hildebrandt MA,  Liang D,  Lu KH,  Wu X,  Bisogna M,  Dao F,  Levine DA,  Cramer DW,  Terry KL,  Tworoger SS,  Stampfer M,  Missmer S,  Bjorge L,  Salvesen HB,  Kopperud RK,  Bischof K,  Aben KK,  Kiemeney LA,  Massuger LF,  Brooks-Wilson A,  Olson SH,  McGuire V,  Rothstein JH,  Sieh W,  Whittemore AS,  Cook LS,  Le ND,  Blake Gilks C,  Gronwald J,  Jakubowska A,  Lubiński J,  Kluz T,  Song H,  Tyrer JP,  Wentzensen N,  Brinton L,  Trabert B,  Lissowska J,  McLaughlin JR,  Narod SA,  Phelan C,  Anton-Culver H,  Ziogas A,  Eccles D,  Campbell I,  Gayther SA,  Gentry-Maharaj A,  Menon U,  Ramus SJ,  Wu AH,  Dansonka-Mieszkowska A,  Kupryjanczyk J,  Timorek A,  Szafron L,  Cunningham JM,  Fridley BL,  Winham SJ,  Bandera EV,  Poole EM,  Morgan TK,  Goode EL,  Schildkraut JM,  Pearce CL,  Berchuck A,  Pharoah PD,  Webb PM,  Chenevix-Trench G,  Risch HA,  MacGregor S
Journal: Hum Genet
Date: 2016 Jul
Branches: CGB, MEB, OD, OEEB
PubMed ID: 27075448
PMC ID: not available
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.