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Title: Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.
Authors: Lu Y,  Cuellar-Partida G,  Painter JN,  Nyholt DR,  Australian Ovarian Cancer Study,  International Endogene Consortium (IEC),  Morris AP,  Fasching PA,  Hein A,  Burghaus S,  Beckmann MW,  Lambrechts D,  Van Nieuwenhuysen E,  Vergote I,  Vanderstichele A,  Doherty JA,  Rossing MA,  Wicklund KG,  Chang-Claude J,  Eilber U,  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,  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,  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,  Gilks CB,  Gronwald J,  Jakubowska A,  Lubiński J,  Gawełko J,  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,  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,  Risch HA,  Goode EL,  Schildkraut JM,  Webb PM,  Pearce CL,  Berchuck A,  Pharoah PD,  Montgomery GW,  Zondervan KT,  Chenevix-Trench G,  MacGregor S
Journal: Hum Mol Genet
Date: 2015 Oct 15
Branches: CGB, MEB, OD, OEEB
PubMed ID: 26231222
PMC ID: PMC4581608
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.