Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis of 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline whole exome or genome sequencing data, and one cohort with imputed array data. At the gene level, our case-control collapsing analysis confirms associations between rare damaging variants in four genes and increased prostate cancer risk: SAMHD1, BRCA2 and ATM at the study-wide significance level (P < 1×10), and CHEK2 at the suggestive threshold (P < 2.6×10).

Somatic BRCA1/2 mutations are associated with a similar survival advantage to their germline counterparts in tubo-ovarian high grade serous carcinoma.

Background: Half of high grade serous tubo-ovarian carcinomas (HGSOC) demonstrate homologous recombination repair (HRR) deficiency, most commonly through germline or somatic pathogenic variants in BRCA1/2 (gBRCA1/2 or sBRCA1/2). gBRCA1/2 is associated with favourable survival, greater response rate to platinum-based chemotherapy, and marked sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. sBRCA1/2 has been assumed to confer a similar clinical phenotype; however, few studies have specifically investigated sBRCA1/2 versus gBRCA1/2 to demonstrate their equivalence.

Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats.

Respiratory function is modulated by circulating steroid hormones. In female rats, steroid hormones fluctuate across the normal estrous cycle and decline with age, similar to human menopause. To determine the influence of steroid hormones, and mimic aspects of age-related reductions in hormones, the ovariectomy model is often employed.

Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).

Estimated reduction in human salmonellosis incidence in Canada from a new government requirement to reduce in frozen breaded chicken products.

Nontyphoidal infections are a leading cause of enteric disease in Canada, most commonly associated with foodborne exposures. Raw frozen breaded chicken products (FBCP) have been implicated in 16 outbreaks between 2017 and 2019. This study quantified the impact of the 1 April 2019 requirement by the Canadian Food Inspection Agency (CFIA) for manufacturers to reduce in raw FBCP.