Background: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. Methods:We searched the PubMed/MEDLINE, Embase, and Cochrane databases.Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively.Subgroup analyses by mutation type (BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in twosided statistical tests. The Prostate. 2019;79:880-895. wileyonlinelibrary.com/journal/pros 880 | Alkhushaym, Fallatah, Althagafi, and Aljadeed have contributed equally to the study and their order of authorship was determined randomly.Results: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier (BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers.Conclusions: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa. K E Y W O R D S BRCA1, BRCA2, meta-analysis, prostate cancer SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Oh M, Alkhushaym N, Fallatah S, et al. The association of BRCA1 and BRCA2 mutations with ...

No abstract

Although Antimicrobial Resistance (AMR) is a worldwide threat, local AMR databases do not exist. Unlike other health disasters, developing containment strategies for AMR cannot be started without a representative, local, updated AMR data. However, Geographical Information Systems (GIS) mapping technology is capable of visualizing AMR data integrated with geographical regions. Due to the absence of AMR databases in Saudi Arabia, we searched Medline and Embase databases from inception until May 28, 2018, including literature that reported AMR data on the most prevalent gram-negative bacterial strains in Saudi Arabia. These data were extracted into Microsoft Excel file and inserted into STATA software, version 13 and ArcMap 10.6 software platform for mapping. We found particularly high levels of AMR in Makkah (Mecca), possibly due to high antibiotic consumption because of the influx of pilgrims, with Pseudomonas aeruginosa isolates showing the highest resistance rate against amikacin, aztreonam, cefepime, ceftazidime, ciprolfloxacin, gentamicin, imipenem, meropenem and pipracillin/tazobactam, and Enterobacteriaceae isolates against cefuroxime, ciprofloxacin, ampicillin, imipenem and ertapenem. The cause is, however, multifactorial since Acinetobacter baumannii isolates showed a variable resistance rate throughout the country. The employment of mapping technology in displaying AMR data extracted from published literature is a practically useful approach, and advanced GIS analyses should help stakeholders create containment strategies and allocate resources to slow down the emergence of AMR.