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.