Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Yi Lu, Gabriel Cuellar-Partida, Jodie N Painter, Dale R Nyholt, Andrew P Morris, Peter A Fasching, Alexander Hein, Stefanie Burghaus, Matthias W Beckmann, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Adriaan Vanderstichele, Jennifer Anne Doherty, Mary Anne Rossing, Kristine G Wicklund, Jenny Chang-Claude, Ursula Eilber, Anja Rudolph, Shan Wang-GohrkeMarc T Goodman, Natalia Bogdanova, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo B Runnebaum, Natalia Antonenkova, Ralf Butzow, Arto Leminen, Heli Nevanlinna, Liisa M Pelttari, Robert P Edwards, Joseph L Kelley, Francesmary Modugno, Kirsten B Moysich, Roberta B Ness, Rikki Cannioto, Estrid Høgdall, Allan Jensen, Graham G Giles, Fiona Bruinsma, Susanne K Kjaer, Michelle A T Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Maria Bisogna, Fanny Dao, Douglas A Levine, Daniel W Cramer, Australian Ovarian Cancer Study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

62 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftHuman Molecular Genetics
Vol/bind24
Udgave nummer20
Sider (fra-til)5955-64
Antal sider10
ISSN0964-6906
DOI
StatusUdgivet - 15 okt. 2015

Citationsformater