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Genome-wide significant risk associations for mucinous ovarian carcinoma.

Publication ,  Journal Article
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 ...
Published in: Nat Genet
August 2015

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2015

Volume

47

Issue

8

Start / End Page

888 / 897

Location

United States

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Microscopy, Fluorescence
  • Humans
  • Homeodomain Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kelemen, L. E., Lawrenson, K., Tyrer, J., Li, Q., Lee, J. M., Seo, J.-H., … Ovarian Cancer Association Consortium, . (2015). Genome-wide significant risk associations for mucinous ovarian carcinoma. Nat Genet, 47(8), 888–897. https://doi.org/10.1038/ng.3336
Kelemen, Linda E., Kate Lawrenson, Jonathan Tyrer, Qiyuan Li, Janet M. Lee, Ji-Heui Seo, Catherine M. Phelan, et al. “Genome-wide significant risk associations for mucinous ovarian carcinoma.Nat Genet 47, no. 8 (August 2015): 888–97. https://doi.org/10.1038/ng.3336.
Kelemen LE, Lawrenson K, Tyrer J, Li Q, Lee JM, Seo J-H, et al. Genome-wide significant risk associations for mucinous ovarian carcinoma. Nat Genet. 2015 Aug;47(8):888–97.
Kelemen, Linda E., et al. “Genome-wide significant risk associations for mucinous ovarian carcinoma.Nat Genet, vol. 47, no. 8, Aug. 2015, pp. 888–97. Pubmed, doi:10.1038/ng.3336.
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. Genome-wide significant risk associations for mucinous ovarian carcinoma. Nat Genet. 2015 Aug;47(8):888–897.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

August 2015

Volume

47

Issue

8

Start / End Page

888 / 897

Location

United States

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Neoplasm Proteins
  • Molecular Sequence Data
  • Microscopy, Fluorescence
  • Humans
  • Homeodomain Proteins