Search Results (9)

Objective: Renal cell carcinoma (RCC) is a rare but severe and aggressive pediatric malignancy. While incidence is uncommon, survival is relatively low with respect to acute lymphocytic leukemia (ALL), AML, lymphoma, ependymoma, glioblastoma, and Wilms Tumor. The pediatric renal cell carcinoma (pRCC) incidence, cumulative incidence (period prevalence), and mortality vary by health disparities’ indicators, namely sex, race, ethnicity, age at tumor diagnosis, and social determinants of health (SDHs) as well as Epigenomic Determinants of Health (EDHs). However, studies are unavailable on some pRCC risk determinants, such as area of residence and socio-economic status (SES). The current study aimed at assessing the temporal trends, cumulative incidence, household median income, urbanity, mortality, and pRCC survival differentials. Materials and Methods: A retrospective cohort design was utilized to examine the event-free survival of children (0–19) with RCC using the Surveillance Epidemiology and End Result Data, 1973–2015. While the time-dependent variable, namely survival months, was utilized, we assessed the predictors of pRCC survival, mainly sex, age at diagnosis, education, insurance status, income, and tumor grade, as prognostic factors. In examining the joint effect of area of residence and race, as an exposure function with time in survival, we utilized the Cox proportional hazard model, while the annual percent change was assessed using a generalized linear model, implying a weighted average. Results: Between 1973 and 2015, there were 174 cases of pRCC, of whom 49 experienced mortality (28.2%). The pRCC cumulative incidence tends to increase with advancing age. A significant survival differential was observed between black/AA children with RCC and their white counterparts. Compared with white children, black/AA children were almost three times as likely to die, hazard ratio (HR) = 2.90, 95% CI = 1.56–5.31, p = 0.001. A survival differential was observed in sex, with males presenting with a 21% increased likelihood of dying, HR = 1.21; 95% CI, 0.69–2.11. In the metropolitan area, the risk of dying was almost three times as likely among black/AA children compared to their white counterparts, HR = 2.78; 95% CI, 1.45–5.43, while in the urban area, the risk of dying was almost four times as likely among black/AA children compared to their white counterparts, HR = 4.18; 95% CI, 0.84–20.80. After controlling for age, sex, education, and insurance, the risk of dying increased amongst black/AA children in metropolitan areas, adjusted HR (aHR) = 3.37, 99% CI = 1.35–8.44. In the urban area, after adjustment for age, sex, and insurance, there was an increased risk of dying for black/AA children, compared with their white counterparts with pRCC, aHR = 8.87, 99% CI = 2.77–28.10. Conclusion: pRCC indicates an increased trend in males and age at diagnosis between 10 and 14, as well as a survival disadvantage among black/AA children, compared with their white counterparts. Additionally, urbanity significantly influences the racial differences in survival. These data are suggestive of the conjoined effect of environment and race in pRCC survival, indicative of further assessment of gene–environment interaction (epigenomics) in incidence, mortality, and survival in pRCC. Full article

Purpose: Racial disparities in infant mortality in the United States persist after adjustment for known confounders of race and mortality association, as well as heterogeneity assessment. Epidemiologic and clinical data continue to show the survival disadvantages of Black/AA children: when Black/AAs are compared to whites, they are three times as likely to die from all-cause mortality. The persistent inability to remove the variance in race–mortality association is partly due to unobserved, unmeasured, and residual confounding, as well as implicit biases in public health and clinical medicine in health equity transformation. This current epidemiologic-perspective explanatory model study aimed to examine the possible explanation of racial differences in U.S. infant mortality using medical misadventures as errors and mistakes, and infants’ involvement in motor vehicular traffic accidents. Materials and Method: Using CDC WONDER ecologic data from 1968 to 2015, we assessed the infant mortality-rate ratio and percent change associated with medical misadventures as well as motor vehicular accidents or trauma. The rate ratio and percent change were estimated using stratification analysis and trend homogeneity, respectively. Results: There was a Black–white racial difference in medical misadventures during the study period. Relative to the years 1968–1978 (rate ratio [RR], 1.43), there was a steady increase in the mortality-rate ratio in 1979–1998 (52%, RR = 1.52), and mortality was more than two times as likely in 1999–2015 (RR = 2.37). However, with respect to motor vehicular accident/trauma mortality, the mortality ratio, although lower among Blacks in 1968–1978 (RR, 0.92), increased in 1979–1998 by 27% (RR = 1.27) but decreased in 1999–2015 (RR, 1.17), though there was still an excess of 17% mortality among Black/AAs. The percent change for medical misadventures indicated an increasing trend from 9.3% in 1998 to 52% in 2015. However, motor vehicular-related mortality indicated a positive trend in 1998 (38.5%) but a negative trend in 2015 (−8.4%). Conclusions: There were substantial race differentials or variances in infant mortality associated with medical misadventures compared to traffic accidents, and Black/AA children relative to whites experienced a survival disadvantage. These comparative findings are suggestive of medical misadventures and motor vehicular trauma as potential explanations for some of the persistent Black–white disparities in overall infant mortality in the U.S. From these findings, we recommend a national effort to address these issues, thus narrowing the observed disparities in the U.S. infant mortality burden among Black/AAs. Full article

Quadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome-amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs. Herein, we analyzed KIFC1 RNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC tumors in three distinct publicly available gene expression datasets and in the breast cancer gene expression database (bc-GenExMiner). KIFC1 levels were significantly higher in AR-low and basal-like TNBCs than in AR-high and non-basal-like TNBCs, irrespective of the stage, grade, tumor size, and lymph node status. KIFC1 levels were also upregulated in AR-low tumors relative to AR-high tumors among Black and premenopausal women with TNBC. High KIFC1 levels conferred significantly shorter overall survival, disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan–Meier analyses. In conclusion, KIFC1 levels may be upregulated in AR-low tumors and, specifically, in those of African descent, wherein it may promote poor outcomes. KIFC1 may be an actionable cancer-cell-specific target for the AR-low TNBC subpopulation and could aid in alleviating racial disparities in TNBC outcomes. Full article

African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20) and Asian (HuH-7) patients. GE exhibited a significantly lower IC₅₀ on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger. Full article

Black/African-American (AA) women, relative to their White/European-American (EA) counterparts, experience disproportionately high breast cancer mortality. Central to this survival disparity, Black/AA women have an unequal burden of aggressive breast cancer subtypes, such as triple-negative breast cancer (ER/PR-, HER2-wild type; TNBC). While TNBC has been well characterized, recent studies have identified a highly aggressive androgen receptor (AR)-negative subtype of TNBC, quadruple-negative breast cancer (ER/PR-, HER2-wildtype, AR-; QNBC). Similar to TNBC, QNBC disproportionately impacts Black/AA women and likely plays an important role in the breast cancer survival disparities experienced by Black/AA women. Here, we discuss the racial disparities of QNBC and molecular signaling pathways that may contribute to the aggressive biology of QNBC in Black/AA women. Our immediate goal is to spotlight potential prevention and therapeutic targets for Black/AA QNBC; ultimately our goal is to provide greater insight into reducing the breast cancer survival burden experienced by Black/AA women. Full article

Tumor genomic profiling (TGP) is used in oncology practice to optimize cancer treatment and improve survival rates. However, TGP is underutilized among Black and African American (AA) patients, creating potential disparities in cancer treatment outcomes. Cost, accuracy, and privacy are barriers to genetic testing, but medical mistrust (MM) may also influence how Black and AA cancer patients perceive TGP. From December 2019 to February 2020, 112 Black and AA adults from two outpatient oncology sites in Philadelphia, PA without a known history of having TGP testing conducted completed a cross-sectional survey. Items queried included sociodemographic characteristics, clinical factors, patient–oncologist relationship quality, medical mistrust, and concerns about TGP. A k-means cluster analysis revealed two distinct psychographic clusters: high (MM-H) versus low (MM-L) medical mistrust. Clusters were not associated with any sociodemographic or clinical factors, except for age (MM-H patients older than MM-L patients, p = 0.006). Eleven TGP concerns were assessed; MM-H patients expressed greater concerns than MM-L patients, including distrust of the government, insurance carriers, and pharmaceutical companies. TGP concerns varied significantly based on level of medical mistrust, irrespective of sociodemographic characteristics. Targeted communications addressing TGP concerns may mitigate disparities in TGP uptake among those with medical mistrust. Full article

Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments. Full article

Background: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black–White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. Methods: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black–White risk differentials. Results: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01–1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93–1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10–2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36–3.88. Conclusion: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States. Full article

Pigmentation plays a vital role in insect survival and reproduction. Many melanin pathway genes have been studied in holometabolous insects; however, they have only been studied in two hemimetabolous insect genera, Oncopeltus and Periplaneta. Here we analyzed three melanin pathway genes (TH, yellow, and aaNAT) using RNA interference (RNAi) in another hemimetabolous insect, namely the twin-spotted assassin bug, Platymeris biguttatus. TH was highly expressed in freshly molted nymphs and adults. TH RNAi resulted in a complete loss of black pigment, with yellow coloration maintained. Therefore, black pigment in this assassin bug is solely generated from the melanin pathway, whereas yellow pigment is generated from other unknown pigmentation pathways. yellow and aaNAT were highly expressed in the white spot of the hemelytra. Downregulation of yellow caused a brown phenotype with high mortality, indicating an important role of yellow functions in cuticle formation and in the process of converting melanin from brown to black. Interestingly, aaNAT RNAi caused not only loss of white pigment, but also loss of yellow and red pigments. This phenotype of aaNAT has not been reported in other insects. Our results provide new information for understanding the melanin pathway in which aaNAT is essential for the formation of colorless patterns. Full article