Mapping the 17q12-21.1 Locus for Variants Associated with Early-Onset Asthma in African Americans.

Rationale: The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives: To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods: We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results: The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions: A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent.

The role of conventional and functional endorectal magnetic resonance imaging in the decision of whether to preserve or resect the neurovascular bundles during radical retropubic prostatectomy.

OBJECTIVE: Because the recovery of erectile function and the avoidance of positive surgical margins are important but competing outcomes, the decision whether to preserve or resect a neurovascular bundle (NVB) during radical prostatectomy (RP) is based on information concerning mostly the presence and location of extracapsular extension (ECE). Conventional endorectal magnetic resonance imaging (e-ctMRI) and functional endorectal MRI (e-ftMRI) of the prostate provide an excellent depiction of the pelvic and prostate anatomy, and are also useful in predicting the presence of prostate cancer as well as ECE, seminal vesicle invasion (SVI) and NVB involvement. Their predictive qualities, however, have shown significant interobserver variability. The aims of this study are to report on accuracy using e-ctMRI and e-ftMRI, and to assess their value in making the decision whether to preserve or resect the NVBs during RP. MATERIAL AND METHODS: From 2004 to 2007, 75 consecutive patients with a biopsy-proven prostate cancer and satisfactory erectile function, who were scheduled to undergo RP, were subjected to e-ctMRI and e-ftMRI before surgery. Interpretation was performed by a highly experienced radiologist blinded to patient clinical data. All patients underwent RP and a nerve-sparing (NS) procedure was considered appropriate if the tumour did not extend outside the capsule in the posterolateral region of the prostate as assessed by the images. RESULTS: An NSRP was performed in 78.7% of patients. Based on the e-ctMRI and e-ftMRI findings, the operative strategy was changed in 44% of patients. The findings favoured NVB preservation in 67% of patients with a high clinical probability of ECE, and opposed NVB preservation in 33% of patients with a low clinical probability of ECE. Based on the final histopathological findings, the surgical plan was successfully changed in all patients. The sensitivity, specificity and accuracy rate were 92%, 100% and 100% for ECE, SVI and NVB involvement, respectively, results which are higher than all other published international standards in this matter. CONCLUSIONS: e-ctMRI and e-ftMRI comprise a sufficient modality in detecting prostate cancer, ECE, SVI and NVB involvement. This technique seems to one of the most sensitive preoperative clinical staging methods for selective patients, and extremely useful for identifying candidates for an NSRP.

A rare case of urinary bladder leiomyosarcoma accompanied by prostate cancer.

Non-urothelial neoplasms of the bladder account for less than 5% of all bladder tumors. Sarcoma constitutes the most usual mesenchymal malignancy of the bladder, with leiomyosarcomas being the most common type of sarcoma in adults. A coexistence of this rare tumor with another malignancy has not been reported, to our knowledge. This report demonstrates a case of high-grade bladder leiomyosarcoma cancer with prostate cancer in a 72-year-old patient. The most striking features of this case include the rapid disease progression that confirms the highly aggressive nature of this uncommon disease.