The distribution of hepatitis B virus exposure and infection in a population-based sample of U.S. Hispanic adults: HEPATOLOGY, Vol. XX, No. X, 2015

Little is known regarding the prevalence and distribution of hepatitis B virus (HBV) infection in United States (US) Hispanics/Latinos. We sought to determine the prevalence of HBV exposure (anti-HBc), active HBV infection (HBsAg), and vaccine-induced HBV immunity (anti-HBs) in US Hispanics/Latinos and consider how these data inform clinical screening recommendations. Our analysis included 11,999 women and men of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based, cross-sectional household survey in four urban communities (Bronx, NY; Miami, FL; Chicago, IL; and San Diego, CA) of US civilian, non-institutionalized self-identifying Hispanic/Latino adults age 18–74. Vaccine-induced immunity was defined as detection of anti-HBs but not anti-HBc. However, if anti-HBc were present it was considered evidence of exposure to HBV, with detection of HBsAg used to distinguish those with active HBV infection. The mean age was 45.7 years and 7,153 were women. Vaccine-induced immunity was greatest among those aged 18–29 years (60.2% in women, 54% in men) and decreased with increasing age, regardless of country of birth. The prevalence of active HBV infection was 0.29% (95% CI: 0.19–0.43%), but varied by country of birth. Those born in the Dominican Republic had the highest prevalence of HBV exposure (20.3% in women, 29.7% in men) and active HBV infection (0.95%)

Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Anaplastic lymphoma kinase (ALK) translocation is an actionable mutation in lung adenocarcinoma. Nonetheless tumour consists of heterogeneous cell subpopulations with diverse phenotypes and genotypes, and cancer cells can actively release extracellular vesicles (EVs) to modulate the phenotype of other cells in the tumour microenvironment. We hypothesized that EVs derived from a drug-resistant subpopulation of cells could induce drug resistance in recipient cells. We have established ALK-translocated lung adenocarcinoma cell lines and subclones. The subclones have been characterized and the expression of EV-RNAs determined by quantitative polymerase chain reaction. The effects of EV transfer on drug resistance were examined in vitro. Serum EV-RNA was assayed serially in two patients prescribed ALK-tyrosine kinase inhibitor (ALK-TKI) treatment. We demonstrated that the EVs from an ALK-TKI-resistant subclone could induce drug resistance in the originally sensitive subclone. EV-RNA profiling revealed that miRNAs miR-21-5p and miR-486-3p, and lncRNAs MEG3 and XIST were differentially expressed in the EVs secreted by the resistant subclones. These circulating EV-RNA levels have been found to correlate with disease progression of EML4-ALK-translocated lung adenocarcinoma in patients prescribed ALK-TKI treatment. The results from this study suggest that EVs released by a drug-resistant subpopulation can induce drug resistance in other subpopulations and may sustain intratumoural heterogeneity

Breast cancer risk in metabolically healthy but overweight postmenopausal women

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin\u27s mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women\u27s Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64-1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88-3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01-4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35-2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64-1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se