The more you look, the more you will find

Abstract

In the current issue of Cancer, Sakamoto et al 1 report on the prevalence of deleterious BRCA1 and BRCA2 germline mutations in an otherwise unselected population of Japanese women with ovarian, fallopian tube, and primary peritoneal cancer. Using a comprehensive next-generation sequencing protocol, this study that found 12 of 95 patients (approximately 13%) carried a deleterious mutation in BRCA1 (5.3%) or BRCA2 (7.4%). This is higher than the rates of approximately 5% to 6% reported by prior Japanese studies. 2,3 This rate also equals those described in Western countries, where 13% to 15% of ovarian cancer patients have been found to harbor a BRCA1/2 mutation. [4][5][6] This study challenges the previously held notion that germline BRCA1/2 mutations are less prevalent in ovarian cancer patients from Asian countries such as Japan.These findings support the concept that the more you look, the more you will find. The 2 prior Japanese studies reporting a lower prevalence of mutations used more limited sequencing approaches.2,3 One study limited its sequencing strategy to the BRCA1 gene only, whereas the other study used an even more restricted approach and sequenced only exon 11 of the BRCA1 gene. In contrast, the current study by Sakamoto et al 1 used a next-generation sequencing protocol to comprehensively analyze the full exons as well as the exon-intron boundaries of the BRCA1 and BRCA2 genes. The current study also used multiplex ligation-dependent probe amplification, a method for detecting large genomic rearrangements, and found a deleterious multiple exon deletion in BRCA2 for 1 patient. Table 1 in this study demonstrates the heterogeneity of the mutations detected, with the 12 different mutations represented by 5 frameshift mutations, 5 nonsense mutations, a missense mutation resulting in a splicing defect, and a genomic rearrangement. The mutations were not clustered in any particular locations but rather were found scattered throughout the 2 genes. This diversity is in line with the fact that more than 1600 and 1800 different mutations have been reported in BRCA1 and BRCA2, respectively, 7 and it supports a more comprehensive approach to mutation detection. The more you look, the more you will find.This study also addresses the important question of whether or not there are clinical characteristics with which we should triage our genetic testing strategies, such as the age of ovarian cancer onset or a family history of cancer. Although BRCA1/2 mutation carriers tend to have a particular ovarian cancer phenotype, there are data to support an unselected and more comprehensive screening approach. Although BRCA1 carriers have an age of ovarian cancer onset that is decades earlier than that of their sporadic counterparts, this is offset by the later age of onset of BRCA2 carriers, which mirrors that of sporadic ovarian cancer development.8 BRCA1/2 carriers may have a family history that is suggestive of a genetic syndrome, but carriers are not infrequently found among those individuals lacking suspicious pedi...

Competing interests at the heart of equine sports medicine ethics: A scoping review and thematic analysis

“…These span management, training techniques, ill treatment, falls, injury and fatality rates and fate after retirement 1 . The ethics of some equine sports medicine veterinary practices have also been criticised in mainstream newspapers in both the United Kingdom 2 and the United States 3 by those outside the veterinary profession, suggesting a need for greater ethical reflection within the profession. Sports medicine ethics is an important and well‐established discipline within human medicine and biomedical ethics.…”