Kar, S.P., Beesley, J., Cox, A. orcid.org/0000-0002-5138-1099 et al. (1 more author) (2016) Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types. Cancer Discovery, 6 (9). pp. 1052-1067. ISSN 2159-8274
Abstract
Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10-8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10-5 in the three-cancer meta-analysis. Significance We demonstrate that combining large-scale genome-wide association meta-analysis findings across cancer types can identify completely new risk loci in common to breast, ovarian, and prostate cancer. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers.
Metadata
Authors/Creators: |
|
||||||
---|---|---|---|---|---|---|---|
Copyright, Publisher and Additional Information: | © American Association for Cancer Research, 2016. This is an author produced version of a paper subsequently published in Cancer Discovery. Uploaded in accordance with the publisher's self-archiving policy. | ||||||
Keywords: | breast cancer; ovarian cancer; prostate cancer; genome-wide association studies; pleiotropy | ||||||
Dates: |
|
||||||
Institution: | The University of Sheffield | ||||||
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
||||||
Funding Information: |
|
||||||
Depositing User: | Symplectic Sheffield | ||||||
Date Deposited: | 22 Jun 2016 09:03 | ||||||
Last Modified: | 18 Jul 2017 11:16 | ||||||
Published Version: | https://doi.org/10.1158/2159-8290.CD-15-1227 | ||||||
Status: | Published | ||||||
Publisher: | American Association for Cancer Research | ||||||
Refereed: | Yes | ||||||
Identification Number: | https://doi.org/10.1158/2159-8290.CD-15-1227 |