Genetic testing for patients at risk of hereditary breast and ovarian cancer.

ABSTRACT: The field of cancer genetic testing has made great advances in correctly identifying patients at risk for hereditary cancer syndromes. These tests, used during a genetic consultation, promote earlier detection of cancer and potentially increase survival. Despite these advancements, a large number of persons at risk for BRCA1/2 mutations remain untested due to a shortage of genetic counselors and lack of clinician knowledge on how to properly screen, identify, and refer patients to genetic counseling. We suggest team-based practices that physician associates/assistants (PAs) and NPs can use in collaboration with genetic counselors. We also explore how PAs and NPs can alleviate the burden on genetic counselors by taking a comprehensive family history, providing elements of counseling, and ordering appropriate genetic tests. This approach maximizes the amount of time the patient spends receiving actual genetic counseling. By creating this collaborative relationship, PAs and NPs can help increase the number of qualifying patients who receive genetic testing and counseling for hereditary breast and ovarian cancer syndromes.

Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice.

Bile acids (BAs) are surfactant molecules that regulate the intestinal absorption of lipids. Thus, the modulation of BAs represents a potential therapy for nonalcoholic fatty liver disease (NAFLD), which is characterized by hepatic accumulation of fat and is a major cause of liver disease worldwide. Cyp8b1 is a critical modulator of the hydrophobicity index of the BA pool. As a therapeutic proof of concept, we aimed to determine the impact of Cyp8b1 inhibition in vivo on BA pool composition and as protection against NAFLD. Inhibition of Cyp8b1 expression in mice led to a remodeling of the BA pool, which altered its signaling properties and decreased intestinal fat absorption. In a model of cholesterol-induced NAFLD, Cyp8b1 knockdown significantly decreased steatosis and hepatic lipid content, which has been associated with an increase in fecal lipid and BA excretion. Moreover, inhibition of Cyp8b1 not only decreased hepatic lipid accumulation, but also resulted in the clearance of previously accumulated hepatic cholesterol, which led to a regression in hepatic steatosis. Taken together, our data demonstrate that Cyp8b1 inhibition is a viable therapeutic target of crucial interest for metabolic diseases, such as NAFLD.-Chevre, R., Trigueros-Motos, L., Castaño, D., Chua, T., Corlianò, M., Patankar, J. V., Sng, L., Sim, L., Juin, T. L., Carissimo, G., Ng, L. F. P., Yi, C. N. J., Eliathamby, C. C., Groen, A. K., Hayden, M. R., Singaraja, R. R. Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice.