Genome-wide significant risk associations for mucinous ovarian carcinoma.

Journal Article (Journal Article)

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 interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Full Text

Duke Authors

Cited Authors

  • Kelemen, LE; Lawrenson, K; Tyrer, J; Li, Q; Lee, JM; Seo, J-H; Phelan, CM; Beesley, J; Chen, X; Spindler, TJ; Aben, KKH; Anton-Culver, H; Antonenkova, N; Australian Cancer Study, ; Australian Ovarian Cancer Study Group, ; Ovarian Cancer Association Consortium,

Published Date

  • August 2015

Published In

Volume / Issue

  • 47 / 8

Start / End Page

  • 888 - 897

PubMed ID

  • 26075790

Pubmed Central ID

  • PMC4520768

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.3336


  • eng

Conference Location

  • United States