Abstract 2546: Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

We have previously reported an association between prostate cancer (PrCa) risk and rs2242652 on 5p15. rs2242652 lies in intron 4 of TERT, which encodes telomerase reverse transcriptase, the catalytic subunit of the telomerase ribonucleoprotein complex. Telomerase catalyzes the de novo addition of telomere repeat sequences on to chromosome ends and thereby counterbalances telomere-dependent replicative senescence. Associations between SNPs in the TERT region and multiple cancer types have been reported; however no correlation has been observed thus far between the cancer-associated SNPs in TERT and gene expression or telomere length. To comprehensively evaluate the association between genetic variation across this region and PrCa we performed a fine-mapping analysis by direct genotyping using either a custom Illumina iSelect array (114 SNPs on iCOGS) or Sequenom MassArray iPlex (25 SNPs) followed by imputation of 1,094 SNPs in 22,301 PrCa cases and 22,320 controls in the PRACTICAL consortium. To determine independently associated variants in this region, we performed multiple stepwise logistic regression analysis; SNPs were included in the model if they were significant at P