Demographic and psychosocial factors associated with limited health literacy in a community-based sample of older Black Americans.

OBJECTIVES: Individuals with limited health literacy often experience suboptimal health outcomes. This study examined the frequency of limited health literacy and demographic and psychosocial factors associated with limited health literacy in a sample of older Black Americans. METHODS: Participants (n = 330) enrolled in a community-based intervention to promote colorectal cancer (CRC) screening completed baseline surveys assessing health literacy with the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) test, CRC awareness, cancer fatalism, Preventive Health Model (PHM) constructs, and demographics. RESULTS: Approximately 52% of participants had limited health literacy, the REALM-R score was 5.4 (SD = 2.7). Univariable correlates of limited health literacy were gender, employment, income, prior screening, cancer fatalism, CRC awareness, and PHM constructs (religious beliefs, salience/coherence, perceived susceptibility). Multivariable correlates of limited health literacy were male gender (OR = 2.3, CI = 1.4-3.8), unable to work (OR = 2.8, CI = 1.3-6.1), lower household income (OR = 3.0, CI = 1.6, 5.5), and higher PHM religious beliefs (OR = 1.1, CI = 1.0-1.2). CONCLUSION: Limited health literacy was associated with multiple complex factors. Interventions should incorporate patient health literacy and low-literacy materials that can be delivered through multiple channels. PRACTICE IMPLICATIONS: Future studies are needed to understand the role of health literacy in an individual's health behavior and the provision of effective healthcare.

Clinical Factors Associated with Urinary Tract Cancer in Individuals with Lynch Syndrome.

BACKGROUND: Lynch syndrome confers markedly increased risks of various malignancies, including urinary tract cancers (UTC; renal pelvis, ureter, bladder, and possibly kidney cancers). It is unknown how to determine which Lynch syndrome carriers are at highest UTC risk. Our aim was to identify clinical factors associated with UTC among Lynch syndrome carriers. METHODS: The study population was a cohort of 52,758 consecutively ascertained individuals undergoing Lynch syndrome testing at a commercial laboratory. Clinical data were obtained from test request forms completed by the ordering provider. Univariate analysis and multivariate logistic regression were performed to identify factors associated with UTC among Lynch syndrome carriers. RESULTS: Compared with noncarriers, Lynch syndrome carriers were significantly more likely to have had UTC (4.1% vs. 1.2%; P < 0.0001). Lynch syndrome-associated UTC was independently associated with male sex [OR 1.95; 95% confidence interval (CI), 1.38-2.76], increased age (OR 2.44 per 10 years; 95% CI, 2.11-2.82), familial burden of UTC (OR 2.69 per first-/second-degree relative with UTC; 95% CI, 1.99-3.63), and pathogenic EPCAM/MSH2 variants (OR 4.01; 95% CI, 2.39-6.72) but not MLH1 variants (OR 1.17; 95% CI, 0.63-2.17), race, or history of other Lynch syndrome-associated malignancy. A total of 143 of 158 (90.5%) Lynch syndrome carriers with UTC had ≥1 of the following characteristics: male sex, EPCAM/MSH2 variants, or family history of UTC; 1,236 of 1,251 (98.8%) Lynch syndrome carriers lacking all of these characteristics had no history of UTC. CONCLUSIONS: Specific clinical factors can reliably identify Lynch syndrome carriers most likely to be at risk for UTC. IMPACT: A predictable subset of Lynch syndrome carriers may be most likely to benefit from UTC surveillance/prevention.

Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.

BACKGROUND: Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. RESULTS: For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancer-associated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. CONCLUSIONS: Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids.

TCR-dependent transformation of mature memory phenotype T cells in mice.

A fundamental goal in cancer research is the identification of the cell types and signaling pathways capable of initiating and sustaining tumor growth, as this has the potential to reveal therapeutic targets. Stem and progenitor cells have been implicated in the genesis of select lymphoid malignancies. However, the identity of the cells in which mature lymphoid neoplasms are initiated remains unclear. Here, we investigate the origin of peripheral T cell lymphomas using mice in which Snf5, a chromatin remodelling-complex subunit with tumor suppressor activity, could be conditionally inactivated in developing T cells. In this model of mature peripheral T cell lymphomas, the cell of origin was a mature CD44hiCD122loCD8⁺ T cell that resembled a subset of memory cells that has capacity for self-renewal and robust expansion, features shared with stem cells. Further analysis showed that Snf5 loss led to activation of a Myc-driven signaling network and stem cell transcriptional program. Finally, lymphomagenesis and lymphoma proliferation depended upon TCR signaling, establishing what we believe to be a new paradigm for lymphoid malignancy growth. These findings suggest that the self-renewal and robust proliferative capacities of memory T cells are associated with vulnerability to oncogenic transformation. Our findings further suggest that agents that impinge upon TCR signaling may represent an effective therapeutic modality for this class of lethal human cancers.