Genome-wide significant risk associations for mucinous ovarian carcinoma

LE Kelemen; K Lawrenson; J Tyrer; Q Li; JM Lee; JH Seo; CM Phelan; J Beesley; X Chen; TJ Spindler; KKH Aben; H Anton-Culver; N Antonenkova; H Baker; EV Bandera; Y Bean; MW Beckmann; M Bisogna; L Bjorge; N Bogdanova; LA Brinton; A Brooks-Wilson; F Bruinsma; R Butzow; IG Campbell; K Carty; J Chang-Claude; YA Chen; Z Chen; LS Cook; DW Cramer; JM Cunningham; C Cybulski; A Dansonka-Mieszkowska; J Dennis; E Dicks; JA Doherty; T Dörk; AD Bois; M Dürst; D Eccles; DT Easton; RP Edwards; U Eilber; AB Ekici; SA Engelholm; PA Fasching; BL Fridley; YT Gao; A Gentry-Maharaj; GG Giles; R Glasspool; EL Goode; MT Goodman; J Grownwald; P Harrington; P Harter; HN Hasmad; A Hein; F Heitz; MAT Hildebrandt; P Hillemanns; E Hogdall; C Hogdall; S Hosono; ES Iversen; A Jakubowska; A Jensen; BT Ji; BY Karlan; M Kellar; JL Kelley; LA Kiemeney; C Krakstad; SK Kjaer; J Kupryjanczyk; D Lambrechts; S Lambrechts; ND Le; AW Lee; S Lele; A Leminen; J Lester; DA Levine; D Liang; J Lissowska; K Lu; J Lubinski; L Lundvall; LFAG Massuger; K Matsuo; V McGuire; JR McLaughlin; I McNeish; U Menon; F Modugno; J Moes-Sosnowska; KB Moysich; SA Narod; L Nedergaard

Journal article

Genome-wide significant risk associations for mucinous ovarian carcinoma

LE Kelemen, K Lawrenson, J Tyrer, Q Li, JM Lee, JH Seo, CM Phelan, J Beesley, X Chen, TJ Spindler, KKH Aben, H Anton-Culver, N Antonenkova, H Baker, EV Bandera, Y Bean, MW Beckmann, M Bisogna, L Bjorge, N Bogdanova Show all

Nature Genetics | Published : 2015

DOI: 10.1038/ng.3336

Abstract

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10-8), rs711830 at 2q31.1 (P = 7.5 × 10-12) and rs688187 at 19q13.2 (P = 6.8 × 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified intera..

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University of Melbourne Researchers

Fiona Bruinsma Author

Ian Campbell Author

Melissa Southey Author

Grants

Awarded by National Institute of Child Health and Human Development

Funding Acknowledgements

We thank all the individuals who took part in this study and all the researchers, clinicians, and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement 223175-HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were supported in part by Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control Consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the consortium website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas (TCGA) Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about TCGA and the investigators and institutions who constitute the TCGA research network can be found on the project website (see URLs).