Germline BRCA mutation in male carriers-ripe for precision oncology?

BACKGROUND: Prostate cancer (PC) is one of the known heritable cancers with individual variations attributed to genetic factors. BRCA1 and BRCA2 are tumour suppressor genes with crucial roles in repairing DNA and thereby maintaining genomic integrity. Germline BRCA mutations predispose to multiple familial tumour types including PC. METHODS: We performed a Pubmed database search along with review of reference lists from prominent articles to capture papers exploring the association between BRCA mtuations and prostate cancer risk and prognosis. Articles were retrieved until May 2017 and filtered for relevance, and publication type. RESULTS: We explored familial PC genetics; discussed the discovery and magnitude of the association between BRCA mutations and PC risk and outcome; examined implications of factoring BRCA mutations into PC screening; and discussed the rationale for chemoprevention in this high-risk population. We confirmed that BRCA1/2 mutations confer an up to 4.5-fold and 8.3-fold increased risk of PC, respectively. BRCA2 mutations are associated with an increased risk of high-grade disease, progression to metastatic castration-resistant disease, and 5-year cancer-specific survival rates of 50 to 60%. CONCLUSION: Despite the growing body of research on DNA repair genes, deeper analysis is needed to understand the aetiological role of germline BRCA mutations in the natural history of PC. There is a need for awareness to screen for this marker of PC risk. There is similarly an opportunity for structured PC screening programs for BRCA mutation carriers. Finally, further research is required to identify potential chemopreventive strategies for this high-risk subgroup.

Evolving surgical techniques of and indications for corneal transplantation in Ontario: 2000 - 2012.

OBJECTIVE: To evaluate trends in indications for and preferred surgical techniques of corneal transplantation in Ontario over a 12-year period. DESIGN: Retrospective review of recipient information forms collected by Eye Bank of Canada (Ontario Division). PARTICIPANTS: Patients who received corneal transplantation in Ontario between 2000 and 2012, totaling 11,725 corneal transplants performed. METHODS: Database containing information collected from recipient information forms maintained by the Eye Bank of Canada (Ontario Division) was reviewed. Corneal transplants performed between July 1, 2000, and June 30, 2012, in Ontario were analyzed. Surgeons complete recipient information forms at the time of corneal transplant surgery. Of the 11,725 available recipient information forms, 10,906 (93%) were sufficiently complete to meet the inclusion criteria and were included in the study. RESULTS: Since 2009, Fuchs endothelial dystrophy overtook pseudophakic corneal edema as the leading indication for corneal transplantation. Since the shift toward lamellar keratoplasty in 2006, there has been a significant decrease in number of corneal transplants performed with penetrating keratoplasty (PKP; p = 0.0016) and a significant increase in Descemet stripping automated endothelial keratoplasty (DSAEK; p = 0.0069) and deep anterior lamellar keratoplasty (p = 0.0108). The gap between number of PKPs and DSAEKs performed each year is progressively narrowing. From July 1, 2011, to June 30, 2012, 514 PKPs were performed compared with 420 DSAEKs. From 2011 to 2012, 83% of corneal transplants indicated by Fuchs endothelial dystrophy were performed with DSAEK, whereas only 13% were performed with PKP. CONCLUSIONS: Six years since initial implementation, partial thickness transplantation continues to increase in popularity. Corneal tissue supply and demand will need to reflect these changes in the field of corneal transplantation.