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

Clinical Management of Chronic Testicular Pain

&lt;i&gt;Aim:&lt;/i&gt; To review the causes and principles and recent concepts in the management of testicular pain. &lt;i&gt;Introduction:&lt;/i&gt; 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. &lt;i&gt;Material and Methods:&lt;/i&gt; 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. &lt;i&gt;Results:&lt;/i&gt; The management of chronic testicular pain remains essentially based on clinical assessment. In recent years there have been advances in the non-surgical 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. &lt;i&gt;Conclusions:&lt;/i&gt; 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 helping them cope with their symptoms. Surgery should not be undertaken lightly for there is no guarantee that there will always be resolution of symptoms and the patient should be counseled accordingly.</jats:p