期刊
CANCER DISCOVERY
卷 6, 期 9, 页码 1052-1067出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-15-1227
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资金
- Cancer Research UK [C1287/A12014, C5047/A7357, C5047/A3354, C5047/A10692, C16913/A6135, C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C8197/A16565]
- European Community [223175 (HEALTH-F2-2009-223175)]
- NIH [CA128978]
- Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]
- U.S. Department of Defense [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- MRC [MR/N003284/1, G0501974, MR/N005813/1] Funding Source: UKRI
- Cancer Foundation Finland sr [150147, 110135] Funding Source: researchfish
- Cancer Research UK [13065, 10118, 15007, 17528, 16565, 14136, 16561, 19170, 12677, 16491] Funding Source: researchfish
- Medical Research Council [MR/N003284/1, G0501974, G1000143, MR/N005813/1, G0401527] Funding Source: researchfish
- National Breast Cancer Foundation [IF-12-06] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10121, NF-SI-0509-10242, NF-SI-0512-10114] Funding Source: researchfish
- Ovarian Cancer Action [OCA6] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
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 GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. 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. (C) 2016 AACR.
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