Genome-wide meta-analyses of breast, ovarian and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types
Genome-wide meta-analyses of breast, ovarian and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types
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.
1052-1067
Kar, Siddhartha P.
763de6ae-485a-4bdb-abfe-bed7ee6b700a
Beesley, Jonathan
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Al Alama, Ali Amin
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Eccles, Diana
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6 September 2016
Kar, Siddhartha P.
763de6ae-485a-4bdb-abfe-bed7ee6b700a
Beesley, Jonathan
0ec7ea7e-d634-48f5-9a1a-89158c82597d
Al Alama, Ali Amin
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Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Kar, Siddhartha P., Beesley, Jonathan and Al Alama, Ali Amin et al.
(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), .
(doi:10.1158/2159-8290.CD-15-1227).
(PMID:27432226)
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.
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Accepted/In Press date: 7 June 2016
e-pub ahead of print date: 17 July 2016
Published date: 6 September 2016
Organisations:
Cancer Sciences
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Local EPrints ID: 405153
URI: http://eprints.soton.ac.uk/id/eprint/405153
ISSN: 2159-8274
PURE UUID: 69410604-5c8f-40d6-82b4-07e341b49bad
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Date deposited: 27 Jan 2017 14:31
Last modified: 16 Mar 2024 02:39
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Author:
Siddhartha P. Kar
Author:
Jonathan Beesley
Author:
Ali Amin Al Alama
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