Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society