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

Complications of vasectomy.

INTRODUCTION: Vasectomy is a common method of sterilisation. However, it is less popular than tubal ligation world-wide. It is also a frequent cause of litigation relating to its complications. This article reviews the early and late risks associated with the procedure. PATIENTS AND METHODS: Data collection was done using the internet to search Medline for obtaining evidence-based medicine reviews. Cross-references were obtained from key articles. Websites of government bodies and medical associations were searched for guidelines relating to vasectomy. DISCUSSION: Early complications include haematoma, wound and genito-urinary infections, and traumatic fistulae. Vasectomy failure occurs in 0-2% of patients. Late recanalisation causes failure in 0.2% of vasectomies. Significant chronic orchalgia may occur in up to 15% of men after vasectomy, and may require epididyectomy or vasectomy reversal. Antisperm antibodies develop in a significant proportion of men post-vasectomy, but do not increase the risk of immune-complex or atherosclerotic heart disease. Similarly, vasectomy does not enhance risk of testicular or prostate cancer. Vasectomy has a lower mortality as compared to tubal occlusion, but is still significantly high in non-industrialised countries because of infections. CONCLUSIONS: Vasectomy, though safe and relatively simple, requires a high level of expertise to minimise complications. Adequate pre-operative counselling is essential to increase patient acceptability of this method of permanent contraception

EAU guidelines on renal cell carcinoma: the 2010 update.

Item does not contain fulltextCONTEXT AND OBJECTIVES: The European Association of Urology Guideline Group for renal cell carcinoma (RCC) has prepared these guidelines to help clinicians assess the current evidence-based management of RCC and to incorporate the present recommendations into daily clinical practice. EVIDENCE ACQUISITION: The recommendations provided in the current updated guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials. EVIDENCE SYNTHESIS: A number of recent prospective randomised studies concerning RCC are now available with a high level of evidence, whereas earlier publications were based on retrospective analyses, including some larger multicentre validation studies, meta-analyses, and well-designed controlled studies. CONCLUSIONS: These guidelines contain information for the treatment of an individual patient according to a current standardised general approach. Updated recommendations concerning diagnosis, treatment, and follow-up can improve the clinical handling of patients with RCC.1 september 201

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)