PURPOSE In studies of men of European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk of aggressive prostate cancer. The contribution of rare coding variation to prostate cancer risk in men of African ancestry has not been established. METHODS We sequenced a panel of 19 DNA repair and cancer predisposition genes in 2,453 African American and 1,151 Ugandan cases and controls with prostate cancer. Rare variants were classified as pathogenic or putatively functionally disruptive and examined in association with prostate cancer risk and disease aggressiveness in gene and pathway-level association analyses. RESULTS Pathogenic variants were found in 75 of 2,098 cases (3.6%) and 31 of 1,481 controls (2.1%; odds ratio [OR], 1.82; 95% CI, 1.19 to 2.79; P = .0044), with the association being stronger for more aggressive disease phenotypes (OR, 3.10; 95% CI, 1.54 to 6.23; P = .0022). The highest risks for aggressive disease were observed with pathogenic variants in the ATM, BRCA2, PALB2, and NBN genes, with ORs ranging from approximately 4 to 15 in the combined study sample of African American and Ugandan men. Rare, nonpathogenic, nonsynonymous variants did not have a major impact on risk of overall prostate cancer or disease aggressiveness. CONCLUSION Rare pathogenic variants in DNA repair genes have appreciable effects on risk of aggressive prostate cancer in men of African ancestry. These findings have potential implications for panel testing and risk stratification in this high-risk population.

The ∼100 known PCa risk variants were shown to effectively stratify PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The 8q24 risk region was also found to be a major contributor to PCa risk in Ugandan men, with the African ancestry-specific risk variant rs72725854 estimated to account for 12% of PCa in this population.

BackgroundIntra-abdominal hypertension (IAH) is defined as a sustained elevation in intra-abdominal pressure (IAP) greater than or equal to 12 mmHg. IAH has been shown to cause organ derangements and dysfunction in the body. Objective screening of IAH is neither done early enough nor at all thus leading to significant morbidity and mortality among surgical patients. The epidemiology and outcome of IAH among surgical patients has not been documented in Uganda. The aim of this study was to determine the prevalence, incidence and outcome of intra-abdominal hypertension among patients undergoing emergency laparotomy.MethodologyProspective observational study, conducted from January to April 2015 among patients undergoing emergency laparotomy. Inclusion criteria was; age >7 yrs, scheduled for emergency laparotomy, able to lie supine. Exclusion Criteria: pregnant, failed urethral catheterization, known cardiac, renal and respiratory disorders. Consecutive sampling was used. IAP, blood pressure, heart rate, respiratory rate, Sp02, Serum creatinine, Serum urea, and Urine output were measured preoperatively and postoperatively at 0, 6, 24 and 48 h. IAH was defined as IAP > 12 mmHg on three consecutive readings 3 min apart.ResultsIn total 192 patients were enrolled. Mean age ± SD was 14.25 (±3.16) yrs in the paediatrics and 34.4(±13.72) yrs in the adults with male preponderance 65 and 80.7 % respectively. The prevalence of IAH was 25 % paediatrics and 17.4 % adults and the cumulative incidence after surgery was 20 % paediatrics and 21 % adults. In paediatrics, IAH was associated with mortality at 0 h postoperatively, RRR = 1:24, 95 % CI (1.371–560.178), p-value 0.048. In adults, the statistically significant outcomes associated with IAH were respiratory system dysfunction RRR1:2.783, p-value 0.023, 95 % CI (1.148–6.744) preoperatively and mortality RRR 1:2.933, p-value 0.034, 95 % CI (1.017–8.464) at 6 h, RRR 1:3.769, p-value 0.033, 95 % CI (1.113–12.760) at 24 h postoperatively.ConclusionThe prevalence and incidence of IAH in the paediatrics and adults group in our study population were high. IAH was associated with mortality in both adult and paediatrics groups and respiratory system dysfunction in adult group. This calls for objective monitoring of intraabdominal pressure in patients undergoing emergency laparotomy with the aim of reducing associated mortality.

The greater incidence of prostate cancer in men of African ancestry remains one of the most important unanswered health disparities globally. No established environmental/lifestyle risk factors have been identified, with the only established risk factors being age, race/ethnicity and family history, all of which implicate genetic susceptibility. GWAS have clearly validated the importance of genetic susceptibility in prostate cancer, with ~100 common risk loci identified to date which in aggregate explain 33% of the familial risk. Genetic studies in African ancestry populations have provided strong evidence for genetic factors in contributing to the greater incidence of prostate cancer in men of African ancestry. To further explore this hypothesis, we conducted a genome-wide association study (GWAS) of prostate cancer among Ugandan men. Specifically, we genotyped the Illumina OncoArray, which includes a 260K GWAS backbone, in 560 prostate cancer cases (119 with Gleason score ≥8) and 480 controls and tested the associations of 448,939 genotyped and 16,396,662 imputed variants with >1% frequency. The most statistically significant variants were observed at the 8q24 risk locus (rs72725854, OR=3.37, P=2.14x10-13). We also observed suggestive signals with 106 variants outside of known risk regions with p-values <10-5 and >10-7. Of the 104 known risk variants, 100 are polymorphic in Uganda men, of which, 66 (66%) had effects that were directionally consistent in their association with prostate cancer risk as previously reported and 8 (8%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs16901979 at 8q24 (OR=1.45, p=0.0001) and rs1512268 at 8p21.2 (OR=1.31, p=0.0087). In addition to these findings, we will also present the results from replication testing of the most significant associations from the GWAS in the Ghana Prostate GWAS Study and the African Ancestry Prostate Cancer Consortium, as well as provide a detailed comparison of polygenic risk models of the known prostate cancer variants between these two African populations, African Africans and men of European ancestry. Citation Format: Zhaohui Du, Alexander Lubmawa, Susan Gundell, Peggy Wan, Nalukenge Cissy, Muwanga Proscovia, Lutalo Moses, Nansereko Deborah, Ndaruhutse Olivia, Katuku Molly, Lubwama Alexander, Rosemary Nassanga, Benson Masaba, Sam Kaggwa, Dan Namuguzi, Vicky Kiddu, Asiimwe Luke, Kuteesa J, Dabanja M. Henry, David Conti, Christopher A. Haiman, Stephen Watya. A genome-wide association study of prostate cancer in Uganda [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1305. doi:10.1158/1538-7445.AM2017-1305

Background: Health related quality of life in patients with urinary bladder cancer is important to measure outcomes beyond morbidity and biological functioning. In 2020, Bladder cancer (BC) contributed to 3% of all cancer worldwide. Globocan 2018 estimated the prevalence of BC in Uganda at 0.8% with a mortality of 75.9%. BC affects the overall quality of life among patients with several factors in uencing this outcome.Our aim was to determine the overall health related quality of life and associated factors among patients with BC in our setting in MNRH in Uganda.Methods: A sample of 111 patients, with histological diagnosis of BC, attending urology clinic or admitted to the urology ward in MNRH were recruited consecutively over a 4-month period. Data was collected by administering the EORTC -QLQ C-30 questionnaire which is a standard intervieweradministered, internationally accepted tool that is validated in Uganda in addition to an associated factors questionnaire. This tool assessed ve domains, with symptoms scale and overall QOL. The mean and standard deviation of the overall quality of life were obtained to determine the mean HRQOL. Using simple linear regression, the factors associated with the mean HRQOL were assessed.Results A total of 111 participants were analyzed and their mean age was 56.6 (SD± 17.3). Most were males 73 (65.8%) and most had attained a primary level of education 55 (49.5%). Most had no comorbidities 65 (58.6%). The mean HRQOL among patients with BC in MNRH was found to be 36.2%