Introduction: Genetic testing in advanced prostate cancer is rapidly moving to become standard of care. Testing for genetic alterations in genes involved in DNA repair pathways, particularly those implicated in the homologous recombination repair (HRR) pathway, in patients with metastatic prostate cancer (mPCa) can inform selection of optimal therapies, as well as provide information about familial cancer risks; however, there are currently no consistent Canadian guidelines in place for genetic testing in mPCa.
Methods: A multidisciplinary steering committee guided the process of an environmental scan to define the current landscape, as well as the perceived challenges, through interviews with specialists from 14 sites across Canada. The challenges most commonly identified include limited testing guidelines and protocols, inadequate education and awareness, and insufficient resources. Following the environmental scan, an expert multidisciplinary working group with pan-Canadian representation from medical oncologists, urologists, medical geneticists, genetic counsellors, pathologists, and clinical laboratory scientists convened in virtual meetings to discuss the challenges in implementation of genetic testing in mPCa across Canada.
Results: Key recommendations from the working group include implementation of germline and tumor HRR testing for all patients with mPCa, with a mainstreaming model in which non-geneticist clinicians can initiate germline testing. The working group defined the roles and responsibilities of the various healthcare providers (HCPs) involved in the genetic testing pathway for mPCa patients. In addition, the educational needs for all HCPs involved in the genetic testing pathway for mPCa were defined.
Conclusions: As genetic testing for mPCa becomes standard of care, additional resources and investments will be required to implement the changes that will be needed to support the necessary volume of genetic testing, to ensure equitable access, and to provide education to all stakeholders.
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http://dx.doi.org/10.5489/cuaj.7954 | DOI Listing |
Genet Epidemiol
January 2025
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).
View Article and Find Full Text PDFEClinicalMedicine
December 2024
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Background: Therapeutic advancements for the polyglutamine diseases, particularly spinocerebellar degeneration, are eagerly awaited. We evaluated the safety, tolerability, and therapeutic effects of L-arginine, which inhibits the conformational change and aggregation of polyglutamine proteins, in patients with spinocerebellar ataxia type 6 (SCA6).
Methods: A multicenter, randomized, double-blind, placebo-controlled phase 2 trial (clinical trial ID: AJA030-002, registration number: jRCT2031200135) was performed on 40 genetically confirmed SCA6 patients enrolled between September 1, 2020, and September 30, 2021.
Rare diseases are collectively common, affecting approximately one in twenty individuals worldwide. In recent years, rapid progress has been made in rare disease diagnostics due to advances in DNA sequencing, development of new computational and experimental approaches to prioritize genes and genetic variants, and increased global exchange of clinical and genetic data. However, more than half of individuals suspected to have a rare disease lack a genetic diagnosis.
View Article and Find Full Text PDFBackground: Alport syndrome (AS) is a multifaceted condition that primarily affects the basement membranes of the kidneys, ears, and eyes. AS is considered the second most common cause of hereditary renal failure, exhibiting varied clinical manifestations across different lifespans. The aim of this study is to investigate the clinical features and genetic profile of AS and to elucidate the genotype-phenotype correlation of AS.
View Article and Find Full Text PDFGlobally, drug-resistant tuberculosis (DR-TB) is responsible for 13% of mortality attributable to antimicrobial resistance. In Ethiopia, extrapulmonary tuberculosis (EPTB) is a significant public health challenge, and drug resistance (DR) in EPTB is often overlooked. In a cross-sectional study conducted between August 2022 and October 2023, we aimed to explore the magnitude of phenotypic drug resistance and identify genetic mutations linked to resistance using 189 Mycobacterium tuberculosis (MTB) isolates cultured from extrapulmonary clinical specimens.
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