Genetic Evaluation for Hereditary Cancer Syndromes Among African Americans: A Critical Review.

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes the available literature on genetic testing for breast, colon, and prostate cancers in the African-American population and explores the disparities in access to genetic testing between non-Hispanic White and African-American patients. This article also addresses the barriers to genetic testing and discrepancies in the uptake of recommendations for hereditary cancer syndromes in the African-American population when compared with non-Hispanic Whites. The review offers practice implications for many healthcare providers and demonstrates gaps in the existing knowledge to be addressed in future studies to help eliminate the persisting health disparities faced by the African-American population.

Erythropoietin Receptor Signaling Supports Retinal Function after Vascular Injury.

The investigation of erythropoietin (EPO) has expanded to include potential nonhematopoietic roles in neural and retinal diseases, including diabetic retinopathy. However, it remains unclear how EPO functions to support the neural retina. Transgenic mice with hypoactive EPO receptor (EPOR) signaling (hWtEPOR) were compared with littermate control mice (WT) to test the role of EPOR signaling under normal conditions and after vascular injury and regrowth into the retina. Although retinal function tested with OptoMotry and electroretinography was comparable to adult (8-week-old) littermate WT mice, hWtEPOR mice had thinner inner and outer plexiform layers and a greater number of amacrine cells. Injury and repair caused by the oxygen-induced retinopathy model reduced visual acuity thresholds, reduced electroretinography amplitudes, and thinned the outer plexiform and inner nuclear layers of both WT and hWtEPOR 8-week-old mice. In hWtEPOR compared with WT mice, scotopic a-wave amplitudes were reduced by injury, despite no change in outer nuclear layer thickness; and peripheral rod, but not cone number, was reduced. Scotopic b-waves were reduced in injured hWtEPOR mice compared with WT, and rod bipolar cell ectopic neurites were increased in both genotypes after injury, suggesting a potential reparative process to preserve connectivity and the b-wave. Normal EPOR signaling appeared important because ectopic neurites and b-waves were lower in the hWtEPOR than WT injured mice.

Correction to: Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy.

The article "Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy", written by "Aaron B. Simmons, Colin A. Bretz, Haibo Wang, Eric Kunz, Kassem Hajj, Carson Kennedy, Zhihong Yang, Thipparat Suwanmanee, Tal Kafri and M. Elizabeth Hartnett", was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 May 2018 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 20 June 2018 to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy.

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

The Black Panther, Masculinity Barriers to Medical Care, and Colorectal Cancer Screening Intention Among Unscreened American Indian/Alaska Native, Black, and White Men.

Objective: To determine if masculinity barriers to medical care and the death from colorectal cancer (CRC) of actor Chadwick Boseman (The Black Panther) influenced CRC early-detection screening intent among unscreened American Indian/Alaska Native (AIAN) and Non-Hispanic-Black (Black) men compared with Non-Hispanic-White (White) men. Methods: Using a consumer-panel, we surveyed U.S. men aged 18-75 years (N = 895) using the 24-item Masculinity Barriers to Medical Care (MBMC) scale. We calculated the median score to create binary exposures to evaluate associations with CRC screening intent and conducted multivariable logistic regression to evaluate independent associations stratified by race/ethnicity. Results: Overall, Black respondents were most likely to have a high MBMC score (55%) compared to White (44%) and AIAN (51%) men (p = 0.043). AIAN men were least likely to report CRC screening intent (51.1%) compared with Black (68%) and White men (64%) (p < 0.001). Black men who reported the recent death of Chadwick Boseman increased their awareness of CRC were more likely (78%) to report intention to screen for CRC compared to those who did not (56%) (p < 0.001). Black men who exhibited more masculinity-related barriers to care were more likely to intend to screen for CRC (OR: 1.76, 95% CI: 0.98-3.16) than their counterparts, as were Black men who reported no impact of Boseman's death on their CRC awareness (aOR: 2.96, 95% CI: 1.13-7.67). Conversely, among AIAN men, those who exhibited more masculinity-related barriers to care were less likely to have CRC screening intent (aOR: 0.47, 95% CI: 0.27-0.82) compared with their counterparts. Conclusions: Masculinity barriers to medical care play a significant role in intention to screen for CRC. While Black men were most likely to state that The Black Panther's death increased their awareness of CRC, it did not appear to modify the role of masculine barriers in CRC screening intention as expected. Further research is warranted to better understand how masculine barriers combined with celebrity-driven health-promotion interventions influence the uptake of early-detection screening for CRC. Impact: Our study provides formative data to develop behavioral interventions focused on improving CRC screening completion among diverse men.

Investigating Racial Differences in Allostatic Load by Educational Attainment among Non-Hispanic Black and White Men.

Education continues to be a key factor contributing to increased access to critical life-improving opportunities and has been found to be protective against Allostatic Load (AL). The purpose of this study was to assess AL among Non-Hispanic (NH) White and NH Black men with the same level of education. We used 1999-2016 National Health and Nutrition Examination Surveys (NHANES) data with an analytical sample of 6472 men (1842 NH Black and 4630 NH White), and nine biomarkers to measure AL, controlling for various demographic and health-related factors. NH Black men had a higher AL score than NH White men (39.1%, 842 vs. 37.7%, 1,975). Racial disparities in AL between NH Black and NH White men who have a college degree or above (PR: 1.49, CI: [1.24-1.80]) were observed. Models posited similar AL differences at every other level of education, although these were not statistically significant. The findings reveal that socioeconomic returns to education and the societal protective mechanisms associated with education vary greatly between White and Black men.

Factors Associated with Colorectal Cancer Prevalence Among Long-Haul Truck Drivers in the United States.

PURPOSE: To determine the age-adjusted association between colorectal cancer (CRC) risk factors and CRC prevalence among long-haul truck drivers (aged 21-85), after adjustment for age. DESIGN: Pooled cross-sectional analysis using Commercial Driver Medical Exam (CDME) data. Setting. National survey data from January 1, 2005, to October 31, 2012. PARTICIPANTS: 47,786 commercial motor vehicle drivers in 48 states. MEASURES: CRC prevalence was the primary outcome; independent variables included demographics, body mass index (BMI), and concomitant medical conditions. ANALYSIS: Kruskal-Wallis tests to analyze continuous variables; Fischer's exact tests to analyze categorical variables; univariate and multivariable logistic regression for rare events (Firth method) to quantify the association between the independent variables of interest and CRC prevalence. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, gender, years with current employer, year of exam, and BMI in a multivariate logistic regression. RESULTS: Many factors were statistically significant. Obesity (OR = 3.14; 95% CI = 1.03-9.61) and increasing age (OR = 1.10 per year; 95% CI = 1.07-1.13) were significantly associated with CRC prevalence. Truckers with 4 or more concomitant medical conditions were significantly more likely to have CRC (OR = 7.03; 95% CI = 1.83-27.03). CONCLUSIONS: Our findings highlight mutable risk factors and represent an opportunity for intervention that may decrease CRC morbidity and mortality among truck drivers, a unique population in the United States estimated to live up to 16 years less than the general population.

Investigation of Differences in Allostatic Load among Black Men by Level of Educational Attainment: High School Graduates Experience the Highest Levels of Stress.

Allostatic load (AL)-the biological assessment of long-term exposure to stress-may explain mortality-rate disparities among non-Hispanic Black (Black) men. We aimed to investigate AL among Black men with equivalent education status after controlling for income. A cross-sectional study was employed to investigate AL among 4113 Black men who participated in the National Health and Nutrition Examination Survey between 1999-2018. A summation of 8 biomarker factors were used to compute AL, differences in socio-demographic characteristics by education status were evaluated, and health behaviors that may influence AL were examined. To determine the high-risk thresholds for each AL component, we examined each component's distribution among NHB men for whom complete biomarker data were available in the NHANES sample. High-risk thresholds were determined as either (1) above the 75th percentile for body mass index (BMI), diastolic blood pressure (DBP), glycated hemoglobin, systolic blood pressure (SBP), total cholesterol, and serum triglycerides; or (2) below the 25th percentile for serum albumin and serum creatinine. Modified Poisson regression models were used to estimate prevalence ratios and their associated 95% confidence intervals for high AL risk while adjusting for potential confounders. Black men with a high school diploma/GED had a greater prevalence of high AL compared with Black men who had other levels of education, and a slightly higher prevalence of high AL compared with Black men who had less than a high school education. Black men with college degrees had a lower prevalence of high AL than Black men with the lowest levels of educational attainment. Researchers must further examine the hidden costs stemming from the interplay between discrimination associated with being Black in America and systemic racism in the educational system-which may be preventing Black men from achieving optimal health.

Factors associated with colorectal cancer screening intent and uptake among adult Non-Hispanic Black men.

Non-Hispanic (NH) Black men in the United States have the lowest five-year colorectal cancer (CRC) survival rate across all racial/ethnic and sex subgroups and are less likely than their NH White counterparts to complete CRC screening. We hypothesized that greater masculinity barriers to medical care (MBMC) would be negatively associated with CRC screening uptake. Employing a survey design, we examined the MBMC scale and other psychosocial factors influencing CRC screening intent and uptake in a sample of 319 NH Black men aged 45 to 75 years residing in Minnesota, Ohio, and Utah. A series of ordinary least squares and logistic regression models were run with intention and uptake as the outcome variable while controlling for various demographic characteristics. Independent variables in all models included average score on the MBMC; CRC screening knowledge, beliefs and values; and barriers to and social support for CRC screening. Social support, marital status, and age were positively associated with CRC screening intention. Increased CRC screening knowledge and older age were associated with a greater likelihood of completing a stool-based screening test for CRC. Fewer masculinity-related and CRC screening barriers were associated with a greater likelihood of undergoing a sigmoidoscopy or colonoscopy. Contrary to our primary hypothesis, lesser MBMC-related perceptions were associated with increased CRC screening uptake among NH Black men. Our findings inform future CRC promotion programs and emphasize the need for multilevel interventions tailored toward this marginalized population to reduce disparities in screening and survival.

Psychometric Properties and Analysis of the Masculinity Barriers to Medical Care Scale Among Black, Indigenous, and White Men.

Non-Hispanic (NH) Black, American Indian/Alaska Native (Indigenous), and NH-White men have the highest colorectal cancer (CRC) mortality rates among all other racial/ethnic groups. Contributing factors are multifaceted, yet no studies have examined the psychometric properties of a comprehensive survey examining potential masculinity barriers to CRC screening behaviors among these populations. This study assessed the psychometric properties of our Masculinity Barriers to Medical Care (MBMC) Scale among NH-Black, Indigenous, and NH-White men who completed our web-based MBMC, Psychosocial Factors, and CRC Screening Uptake & Intention Survey. We conducted exploratory factor analysis on a sample of 254 men and multivariate analysis of variance (MANOVA) on a separate sample of 637 men nationally representative by age and state of residence. After psychometric assessment, the MBMC scale was reduced from 24 to 18 items and from six to four subscales. NH-Black men's mean scores were lowest on three of four subscales (Being Strong, Negative and Positive Attitudes) and highest on the Acknowledging Emotions subscale. Compared with both Indigenous and NH-White men, NH-Black men had significantly lower Negative Attitudes subscale scores and significantly higher scores on the Acknowledging Emotions subscale. Compared with both Indigenous and NH-Black men, NH-White men had significantly higher Being Strong and Positive Attitudes subscales scores. This study expands on previous research indicating that, among racialized populations of men, endorsement of traditional masculine ideologies influences engagement in preventive health behaviors. Our scale can be tailored to assess attitudes to screening for other cancers and diseases that disproportionately burden medically underserved populations.