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abstract
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.
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