Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

A Bone Scan Is Valuable for Primary Staging of Newly Diagnosed Prostate Cancer in a Low-Resource Setting (Nigeria).

Objective: There is a paucity of information on bone scanning for prostate cancer from low-resource countries. This study evaluated the role of bone scan in the primary staging of newly diagnosed prostate cancer in one such setting. Methods: A retrospective analysis of 126 men with newly diagnosed prostate cancer undergoing an initial staging bone scan between January 2017 and December 2020 was carried out at a regional nuclear medicine center in Nigeria. Bone scan results were analyzed according to age, serum level of baseline prostate-specific antigen (PSA), and Gleason score. Equivocal scans and patients with no Gleason score or baseline PSA were excluded from the analysis. p < 0.05 was said to be significant statistically. Results: Of 111 patients (aged 38-84 years, median 66 years), who met the inclusion criteria, 26 (23%) men had evidence of bony metastases as shown by a positive bone scan. Higher PSA levels and Gleason scores were associated with an increased risk of a positive bone scan, p < 0.001. No patient with a PSA level < 20 ng/mL and a Gleason score of < 7 had a positive bone scan. Conclusion: The role of bone scanning in staging newly diagnosed prostate cancer patients in Nigeria is consistent with global reports. Our study confirms that a bone scan finding is well associated with the risk classification using PSA and Gleason score in our population.

Erectile Dysfunction Among Men Attending Surgical Outpatients Department in a Tertiary Hospital in South-Western Nigeria.

BACKGROUND: Erectile dysfunction is becoming a public health issue with high incidences reported in community studies. OBJECTIVE: To evaluate the characteristics and outcome of treatment in men with erectile dysfunction in a tertiary center in Ibadan southwestern Nigeria. METHODS: Data of men with erectile dysfunction was retrieved between July 2004 and June 2014 and analyzed using SPSS version 16 statistical software. RESULTS: Eighty-nine men with erectile dysfunction were managed which constituted 2% of all urological cases seen during the study period. Their median and mean ages were 39 years and 39.6 ± 1.2SD (range 19-76 years). The peak age incidence at 30-44 years was 41.6% and reduced with increasing age after 65 years to 4.5%. The etiologies were psychogenic in 55%, organic in 27%, idiopathic in 17% and 1% was familial. 67.5%, 31.5% and 3.4% were married, single and separated respectively. Seventy percent neither smoked cigarette nor drank alcohol, 21.3% drank alcohol and 9% took both alcohol and smoked cigarette. Seventy seven and half percent of men presented within 5 years of their symptom. The treatments offered were PDE type 5 inhibitors alone or in combination with psychotherapy or modification of medications. The outcome of these treatments ranged from 89% to 91% success rate. CONCLUSION: The number of men with erectile dysfunction managed in the tertiary hospital is very low though the outcome of treatment is within acceptable range. Increase public enlightenment may encourage increase hospital patronage and access to the available treatments for erectile dysfunction.

Bilateral double ureters with bladder neck diverticulum in a nigerian woman masquerading as an obstetric fistula.

A 43-year-old woman presented with 20-year history of leakage of urine per vaginam. She had one failed repair attempt. Pelvic examination with dye test showed leakage of clear urine suggestive of ureterovaginal fistula. The preoperative intravenous urogram revealed duplex ureter and cystoscopy showed normally cited ureteric orifices with two other ectopic ureteric openings and bladder diverticula. The definitive surgery performed was ureteric reimplantation (ureteroneocystostomy) of the two distal ureteric to 2 cm superiolateral to the two normal orifices and diverticuloplasty. There was resolution of urinary incontinence after surgery. Three months after surgery, she had urodynamic testing done (cystometry), which showed 220 mLs with no signs of instability or leakage during filling phase but leaked on coughing at maximal bladder capacity. This is to showcase some diagnostic dilemma that could arise with obstetric fistula, which is generally diagnosed by clinical assessment.

Urethral obstruction from dislodged bladder diverticulum stones: a case report.

BACKGROUND: Secondary urethral stone although rare, commonly arises from the kidneys, bladder or are seen in patients with urethral stricture. These stones are either found in the posterior or anterior urethra and do result in acute urinary retention. We report urethral obstruction from dislodged bladder diverticulum stones. This to our knowledge is the first report from Nigeria and in English literature. CASE PRESENTATION: A 69 year old, male, Nigerian with clinical and radiological features of acute urinary retention, benign prostate enlargement and bladder diverticulum. He had a transurethral resection of the prostate (TURP) and was lost to follow up. He re-presented with retained urethral catheter of 4 months duration. The catheter was removed but attempt at re-passing the catheter failed and a suprapubic cystostomy was performed. Clinical examination and plain radiograph of the penis confirmed anterior and posterior urethral stones. He had meatotomy and antegrade manual stone extraction with no urethra injury. CONCLUSIONS: Urethral obstruction can result from inadequate treatment of patient with benign prostate enlargement and bladder diverticulum stones. Surgeons in resource limited environment should be conversant with transurethral resection of the prostate and cystolithotripsy or open prostatectomy and diverticulectomy.

Daycase urology at Ibadan, Nigeria: a ten year review.

INTRODUCTION: The objective of the study was to report the extent of urological surgeries performed as day cases in a major tertiary hospital in Ibadan and document the outcome. METHODS: We retrospectively reviewed the data of all urologic patients treated at the day-case theatre between January 2000 and December 2009. The parameters evaluated were: age, diagnosis, type of surgery/procedure, anaesthesia administered and the rank of the surgeon. Day case endoscopic procedures as well as prostate biopsies were excluded from the study. RESULTS: In total, 1292 patients were managed, 290 (22.4%) were children aged between 5 days and 15 years while 1002 (77.6%) adults aged between 17 years and 91 years. The majority of the procedures were carried out by the senior registrars (1169 cases, 90.5%) and consultants were involved in 123 cases (9.5%). General anaesthesia was primarily used in children (158 children vs. 4 adults), while local anaesthesia was used only in adults. 131 (45.2%) children had no anaesthesia for circumcision. The most common procedures performed in adults were varicocelectomy (426 cases, 42.5%), orchidectomy (332 cases, 33.1%), testicular biopsy (120 cases, 12.0%). While in children male circumcision (231 cases, 79.7%) was the main procedure performed. CONCLUSION: The day-case theatre is still suitable for day case urologic procedure in our setting. The common procedures are varicocelectomy, orchidectomy, and open testicular biopsy in the adults. While in children, male circumcision is commonly carried out.