Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome.

BRCA1-associated protein-1 (BAP1) is a recognised tumour suppressor gene. Germline BAP1 pathogenic/likely pathogenic variants are associated with predisposition to multiple tumours, including uveal melanoma, malignant pleural and peritoneal mesothelioma, renal cell carcinoma and specific non-malignant neoplasms of the skin, as part of the autosomal dominant BAP1-tumour predisposition syndrome. The overall lifetime risk for BAP1 carriers to develop at least one BAP1-associated tumour is up to 85%, although due to ascertainment bias, current estimates of risk are likely to be overestimated. As for many rare cancer predisposition syndromes, there is limited scientific evidence to support the utility of surveillance and, therefore, management recommendations for BAP1 carriers are based on expert opinion. To date, European recommendations for BAP1 carriers have not been published but are necessary due to the emerging phenotype of this recently described syndrome and increased identification of BAP1 carriers via large gene panels or tumour sequencing. To address this, the Clinical Guideline Working Group of the CanGene-CanVar project in the United Kingdom invited European collaborators to collaborate to develop guidelines to harmonize surveillance programmes within Europe. Recommendations with respect to BAP1 testing and surveillance were achieved following literature review and Delphi survey completed by a core group and an extended expert group of 34 European specialists including Geneticists, Ophthalmologists, Oncologists, Dermatologists and Pathologists. It is recognised that these largely evidence-based but pragmatic recommendations will evolve over time as further data from research collaborations informs the phenotypic spectrum and surveillance outcomes.

Emergency Department visits for depression following police killings of unarmed African Americans.

Previous literature on racism and adverse mental health largely focuses on individual-level exposures. We investigate whether and to what extent structural racism, as measured by police killings of unarmed African Americans, affect a severe and acute mental health outcome among African Americans: depression-related Emergency Department (ED) visits. We used police killings of unarmed African Americans as our exposure and depression-related ED visits (per 100,000 population) as our outcome. We examined the relation across 75 counties from five US states between 2013 and 2015 (2700 county-months). Linear fixed effect analyses controlled for time-invariant county-factors as well as the number of hospitals and arrests for violent crimes (per 100,000 population). Police killings of unarmed African Americans correspond with an 11% increase in ED visits per 100,000 population related to depression among African Americans in the concurrent month and three months following the exposure (p < 0.05). Researchers and policymakers may want to consider prevention efforts to reduce racial bias in policing and implement surveillance of fatal police encounters. These encounters, moreover, may worsen mental health and help-seeking in the ED among African Americans not directly connected to the encounter.

Advances in the recognition and management of hereditary cancer.

INTRODUCTION: Constitutional mutations in genes controlling DNA repair, cell-cycle regulation and cell apoptosis can determine an individual's tendency to develop cancer. Hereditary cancer predisposition syndromes present with multiple cancers at a young age and underlie a significant burden of morbidity and mortality. Recent advances in the recognition and management of hereditary cancer will be illustrated with specific examples of developments in diagnosis and treatment. SOURCES OF DATA: Key recent published literature. AREAS OF AGREEMENT: The identification of individuals with hereditary cancer offers important opportunities for cancer prevention, early intervention and personalized management. AREAS OF CONTROVERSY: Individuals at risk of hereditary cancer remain under-recognized. There is a need to develop evidence-based guidelines for the recognition and management of hereditary cancer predisposition conditions. GROWING POINTS: The study of Mendelian cancer susceptibility syndromes has added to our understanding of hereditary and sporadic cancers and facilitated the development of targeted agents directed against cancer-driving mutations. Increasingly, cancer patients with constitutional gene mutations treated with targeted therapies have improved clinical outcomes. AREAS FOR TIMELY RESEARCH: Building the infrastructure to enable constitutional gene mutation testing to become integrated into routine cancer care, including the parallel development of robust referral pathways alongside genomic sequencing technologies.