Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

A ten-year observational study of the use of two-way catheters post-transurethral resection of the prostate without the use of post-op irrigation

Background: Over 15,000 transurethral resections of the prostate (TURP) are performed annually in the United Kingdom. It is therefore vital that every aspect of peri-operative care be optimised. Our centre favours the use of two-way catheters post-operatively without the use of continuous bladder irrigation (CBI). Objectives: To evaluate our practice of using two-way catheters without irrigation post-TURP and to determine impact on patient care compared with standard three-way catheterisation. Our primary outcome was duration of admission, but multiple secondary outcomes were also analysed. Design, setting, and participants: This was a prospective observational study. Every patient undergoing TURP at our centre from 2009 to 2019 was included. Following TURP patients were catheterised with two-way catheters. Prospective patient data were collected pertaining to peri-operative factors. These data were then compared with the data published in the literature. Results: 687 patients underwent TURP at our centre between 2009 and 2019. The average age of patients was 71.42 (±7.89). 87.17% (n = 598) had two-way catheters placed post-operatively. Average duration of admission was 1.61 (±1.35) days, increasing to 2.20 days if patients required three-way catheters or 2.53 days if requiring CBI. TWOC was successful in 97.71% of patients. Complication rate was 8.73% (n = 60). When compared with other centres, our method reduced lengths of admission and transfusion rates (1.6 days versus 3.1 days and 0.87% versus 2.83%, respectively). Conclusion: Our method is safe and is associated with a reduced length of admission. We recommend this practice to the wider urological community. Patient summary: This study looked at whether there was any impact on patients if two-way catheters were used following TURP. We found that use of two-way catheters reduced length of admission and duration of catheterisation. We also found that it did not increase likelihood of peri-operative complications in comparison with other centres

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)