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

Clinical Management of Chronic Testicular Pain

Introduction Chronic testicular pain is a common presenting problem in urology and general practitioner's clinics. There seems to be an increase in such referrals due to public awareness of testicular cancer. With an increase in easily available information by the media the last decade has seen an explosion in magazines focusing on men's health and 'men's problems'. Similarly the internet abounds with easily accessible websites devoted to health concerns giving voluminous information to consult. A major side effect of this however is anxiety about one's own problems, encouraging the individual to seek further medical advice and reassurance. Chronic orchialgia is defined as an intermittent or constant testicular pain, unilateral or bilateral, lasting for over 3 months that interferes significantly with the patient's daily activities Key Words Orchialgia ؒ Testicular pain, chronic ؒ Genitourinary surgery Abstract Aim: To review the causes and principles and recent concepts in the management of testicular pain. Introduction: Chronic testicular pain is a common presenting symptom in genitourinary surgery. Due to increased awareness of testicular cancer and in men's health more cases are likely to be referred. Material and Methods: A literature search was made for abstracts, original papers and review articles in the Cochrane Database, Medline and medical textbooks using the words 'testicular pain' and orchialgia to find the causes and mechanisms of testicular pain. The management and algorithm have been structured on evidence-based management strategies. Results: The management of chronic testicular pain remains essentially based on clinical assessment. In recent years there have been advances in the nonsurgical management of testicular pain mainly because of the emergence of pain relief as a specialty. However, in some cases pain control is a problem and may ultimately conclude with orchiectomy. Conclusions: The management of chronic testicular pain includes a careful assessment of testicular and extratesticular causes. Relief of symptoms is not always possible and gaining an insight into the patient's concerns and empathizing with their condition is paramount in help

Haematospermia – A Systematic Review

Haematospermia (or haemospermia) is a distressing symptom in sexually active men. In most cases, it is caused by non-specific inflammation of the prostate and seminal vesicles. In a small percentage of men, however, it may be a manifestation of genito-urinary or systemic malignancy, in particular prostate cancer. The purpose of this review is to explain the causes and management of patients with haematospermia

The risk of prostate cancer amongst Black men in the United Kingdom: The PROCESS cohort study

Objectives: It is known that African American men have a greater risk of prostate cancer than white men. We investigated whether this was true for first-generation black Caribbean and black African men in the United Kingdom. Methods: A clinical cohort study design recruiting all cases of prostate cancer diagnosed over a 5-yr period and residing in defined areas of London and Bristol. We calculated the age-standardised incidence rates and relative risk for all black men, and black Caribbean and black African men versus white men. Results: Black men had higher age-adjusted rates of prostate cancer (166 per 100,000, 95% confidence interval [95%CI], 151-180 per 100,000) than white men (56.4 per 100,000, 95%CI, 53.3-59.5 per 100,000). The relative risks for all black, black Caribbean, and black African men were 3.09 (95%CI, 2.79-3.43; p < 0.0001), 3.19 (95%CI, 2.85-3.56; p < 0.0001) and 2.87 (95%CI, 2.34-3.53; p < 0.0001), respectively. There was no strong evidence that the rates for black Caribbean differed from black African men. The higher risk in black men compared with white men was more apparent in younger age groups (p value for interaction <0.001). Conclusions: Black men in the United Kingdom have substantially greater risk of developing prostate cancer compared with white men, although this risk is lower than that of black men in the United States. The similar rates in black Caribbean and black African men suggest a common genetic aetiology, although migration may be associated with an increased risk attributable to a gene-environment interaction.7 page(s

The risk of prostate cancer amongst South Asian men in southern England : the PROCESS cohort study

OBJECTIVE: To reinvestigate whether South Asian men in the UK are at lower risk of being diagnosed with prostate cancer in a UK-based retrospective cohort study and to examine possible reasons that may explain this. PATIENTS AND METHODS: The catchment areas were predefined in four areas of southern England, and age- and race-specific populations for those areas taken from census data. Cases were ascertained through review of multiple hospital sources, while race, other demographic factors, and medical history were determined using questionnaires sent to the men, hospital records review and death certificates. The South Asian group included men of Indian, Bangladeshi and Pakistani origin. RESULTS: There was modest evidence of lower prostate cancer rates in South Asian men compared with their White neighbours (age-adjusted rate ratio 0.81; 95% confidence interval 0.65-1.00). This difference did not reflect less use of prostate-specific antigen (PSA) testing or differences in clinical features at presentation. CONCLUSION: This study provides evidence of a lower incidence of prostate cancer amongst South Asian men living in England, in comparison with their White counterparts. If anything, South Asian men presented with clinical features of earlier disease suggesting that the reduced risk is unlikely to be an artefact of poorer access to health care.6 page(s

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