Genetic Testing Among Patients with High-Risk Breast, Ovarian, Pancreatic, and Prostate Cancers.

BACKGROUND: The National Comprehensive Cancer Network recommends genetic testing in patients with potentially hereditary breast, ovarian, pancreatic, and prostate cancers (HBOPP). Knowledge of genetic mutations impacts decisions about screening and treatment. METHODS: A retrospective cohort study of 28,586 HBOPP patients diagnosed from 2013 to 2019 was conducted using a linked administrative-cancer database in the Seattle-Puget Sound SEER area. Guideline-concordant testing (GCT) was assessed annually according to guideline updates. Frequency of testing according to patient/cancer characteristics was evaluated using chi-squared tests, and factors associated with receipt of genetic testing were identified using multivariable logistic regression. RESULTS: Testing occurred in 17% of HBOPP patients, increasing from 9% in 2013 to 21% in 2019 (p < 0.001). Ovarian cancer had the highest testing (40%) and prostate cancer the lowest (4%). Age < 50, female sex, non-Hispanic White race, commercial insurance, urban location, family history of HBOPP, and triple negative breast cancer (TNBC) were associated with increased testing (all p < 0.05). GCT increased from 38% in 2013 to 44% in 2019, and was highest for early age at breast cancer diagnosis, TNBC, male breast cancer, and breast cancer with family history of HBOPP (all > 70% in 2019), and lowest for metastatic prostate cancer (6%). CONCLUSIONS: The frequency of genetic testing for HBOPP cancer has increased over time. Though GCT is high for breast cancer, there are gaps in concordance among patients with other cancers. Increasing provider and patient education, genetic counseling, and insurance coverage for testing among HBOPP patients may improve guideline adherence.

The contribution of small cryptic plasmids to the antibiotic resistance of enteropathogenic Escherichia coli E2348/69.

Two uncharacterized small cryptic plasmids (SCPs) were isolated from enteropathogenic Escherichia coli strain E2348/69. Genomic DNA sequence analysis of both SCPs indicated that the smaller plasmid, p5217, encoded several mobilization genes, whereas the larger plasmid, p6148, encoded several putative antibiotic resistance determinants. Complementation analysis showed that p6148 encodes functional streptomycin resistance genes but, owing to the presence of several frameshift mutations, a nonfunctional sulfonamide resistance determinant. A plasmid similar to p6148 has previously been shown to confer a slight growth advantage on E. coli. However, we were unable to observe any significant growth advantage in different E. coli strains transformed with p6148. The p6148 DNA sequence is homologous in sequence and arrangement to DNA from other plasmid families, including large conjugative plasmids and SXT integrative and conjugative elements. This study suggests that gene clusters of the sul2-strAB antibiotic resistance genes are widespread and highly transferable, owing to their presence in a wide variety of mobile genetic elements.