The Genetic Paradigm of Hereditary Breast and Ovarian Cancer (HBOC) in the Afro-Caribbean Population.

Differences in tumor biology and genetic predisposition have been suggested as factors influencing overall survival and increased mortality in Black breast and ovarian cancer patients. Therefore, it is key to evaluate genetic susceptibilities in Afro-Caribbean patients because the black population in the US is not homogeneous. Identifying a high incidence of hereditary breast and ovarian cancer (HBOC) in Afro-Caribbean countries can lead to understanding the pattern of inherited traits in US-Caribbean immigrants and their subsequent generations. The paucity of projects studying the genetic landscape in these populations makes it difficult to design studies aimed at optimizing screening and prophylaxis strategies, which in turn, improve survival and mortality rates. This scoping review identifies and categorizes current research on the genetic paradigm of HBOC in the Afro-Caribbean population. We performed an evaluation of the evidence and generated a summary of findings according to preferred reporting items for systematic review and meta-analysis (PRISMA) Extension for Scoping Reviews guidelines. We included articles that assessed the incidence and prevalence of pathologic germline mutations and experience/barriers for genetic testing in Afro-Caribbean Countries and US-Caribbean patients. Our results highlight countries where genetic landscapes remain severely understudied and support recommending multigene testing in Caribbean-born patients. They highlight a need for further research on the genetic paradigm of HBOC in the Afro-Caribbean population to improve genetic testing/counseling and the subsequent adoption of early detection and risk reduction strategies.

A machine learning one-class logistic regression model to predict stemness for single cell transcriptomics and spatial omics.

Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic features from non-transformed stem cells to identify dedifferentiated cell states in tumors. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. This machine learning model identified stem-like cell populations not identified in single cell or spatial transcriptomic analysis using existing methods. For the first time, we demonstrate the application of a ML tool across five emerging spatial transcriptomic and proteomic technologies to identify oncogenic stem-like cell types in the tumor microenvironment.

Increasing diversity of functional genetics studies to advance biological discovery and human health.

In this perspective we discuss the current lack of genetic and environmental diversity in functional genomics datasets. There is a well-described Eurocentric bias in genetic and functional genomic research that has a clear impact on the benefit this research can bring to underrepresented populations. Current research focused on genetic variant-to-function experiments aims to identify molecular QTLs, but the lack of data from genetically diverse individuals has limited analyses to mostly populations of European ancestry. Although some efforts have been established to increase diversity in functional genomic studies, much remains to be done to consistently generate data for underrepresented populations from now on. We discuss the major barriers for this continuity and suggest actionable insights, aiming to empower research and researchers from underserved populations.

Unique Considerations in Early Detection, Risk, and Awareness of Endometrial Cancer in Black Women.

Endometrial cancer is the most common gynecologic cancer in the United States. Over the last several decades, the incidence of aggressive tumors, and thus the rate of death from disease, has increased significantly. The population most affected by these epidemiologic shifts are Black women. Symptom awareness, lack of treatment access, and failure of providers to provide guideline-concordant care are just some of the drivers behind these changes. Race as a social construct has historically categorized women into groups that are not reflective of the nuanced personalization that is required for cancer prevention strategies and targeted cancer treatments. There is, however, an increasing understanding that disaggregation by place of birth and social context are important to understand care-seeking behaviors, genetic drivers of disease, and factors that lead to deleterious outcomes. In this review, we will focus on specific individual-level influences that impact disease diagnosis and care-seeking among Black women, recognizing that the global disparities which exist in this disease encompass multiple domains. Such considerations are crucial to understanding drivers of self-efficacy and to develop programs for knowledge awareness and empowerment within a framework that is both useful and acceptable to these diverse communities at risk.

Challenges and Opportunities in Building a Global Representative Single-Cell and Spatial Atlas in Cancer.

SUMMARY: Cancer health disparities are complex and a mixture of factors that need to be accounted for in both our planning, implementation, and execution across all researchers, especially in single-cell and spatial technologies, which have a higher burden for adoption in low- and middle-income countries. This commentary tackles the hurdles these technologies face in creating a diverse, representative atlas of cancer and is a call to arms for a strategic plan toward inclusivity across all global populations.

Intra-racial disaggregation reveals associations between nativity and overall survival in women with endometrial cancer.

OBJECTIVE: Prior studies have demonstrated survival differences between Black women with endometrial cancer (EC) born in the US and Caribbean. Our objective was to determine if country of birth influences EC overall survival (OS) in disaggregated subpopulations of Black women. METHODS: Using the Florida Cancer Data System, women with EC diagnosed from 1981 to 2017 were identified. Demographic and clinical information were abstracted. Women who self-identified as Black and born in the US (USB), Jamaica (JBB), or Haiti (HBB) were included. Statistical analyses were performed using chi-square, Cox proportional hazards models, and Kaplan-Meier methods with significance set at p < 0.05. RESULTS: 3817 women met the inclusion criteria. Compared to USB, JBB and HBB had more high-grade histologies, more advanced stage disease, had a greater proportion of uninsured or Medicaid insured, and had a higher proportion of women who received chemotherapy (all p < 0.05). In multivariate analyses, age (HR 1.03 [1.02-1.05]), regional stage (HR 1.52 [1.22-1.89]), distant stage (HR 3.73 [2.84-4.89]), lymphovascular space invasion (HR 1.96 [1.61-2.39]), receipt of surgery (HR 0.47 [0.29-0.75]), and receipt of chemotherapy (HR 0.77 [0.62-0.95]) were independently associated with OS. Compared to USB, Haitian nativity was an independent negative predictor of OS when evaluating all histologies together (HR 1.54 [1.18-2.00]) and for endometrioid EC specifically (HR 1.77 [1.10-2.83]). Among women with serous EC, HBB had markedly worse median OS (18.5 months [13.4-46.5]) relative to USB (29.9 months [26.3-35.9]) and JBB (41.0 months, [34.1-82.6], p = 0.013). CONCLUSION: Country of birth is associated with endometrial cancer survival in Black women, with HBB demonstrating worse outcomes.

Differences in Cervical Cancer Outcomes by Caribbean Nativity in Black and White Women in Florida.

OBJECTIVE: Racial disparities among women with cervical cancer have been reported but are understudied in Caribbean immigrants. The objective of this study is to describe the disparities in clinical presentation and outcomes between Caribbean-born (CB) and US-born (USB) women with cervical cancer by race and nativity. METHODS: An analysis of the Florida Cancer Data Service (FCDS), the statewide cancer registry, was performed to identify women diagnosed with invasive cervical cancer between 1981 and 2016. Women were classified as USB White or Black and CB White or Black. Clinical data were abstracted. Analyses were done using chi square, ANOVA, Kaplan-Meier and Cox proportional hazards models, with significance set at P < .05. RESULTS: 14 932 women were included in the analysis. USB Black women had the lowest mean age at diagnosis, while CB Black women were diagnosed at later stages of disease. USB White women and CB White women had better OS (median OS 70.4 and 71.5 months, respectively) than USB Black and CB Black women (median OS 42.4 and 63.8 months, respectively) (P < .0001). In multivariable analysis, relative to USB Black women, CB Blacks (HR .67, CI .54-.83), and CB White (HR .66, CI .55-.79) had better odds of OS. White race among USB women was not significantly associated with improved survival (P = .087). CONCLUSION: Race alone is not a determinant of cancer mortality in women with cervical cancer. Understanding the impact of nativity on cancer outcomes is crucial to improve health outcomes.

Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy - non-mitotic mechanisms of paclitaxel.

Taxanes and CDK4/6 inhibitors (CDK4/6i) are two families of successful anti-mitotic drugs used in the treatment of solid tumors. Paclitaxel, representing taxane compounds, has been used either alone or in combination with other agents (commonly carboplatin/cisplatin) in the treatment of many solid tumors including ovarian, breast, lung, prostate cancers, and Kaposi's sarcoma. Paclitaxel has been routinely prescribed in cancer treatment since the 1990s, and its prominent role is unlikely to be replaced in the foreseeable future. Paclitaxel and other taxanes work by binding to and stabilizing microtubules, causing mitotic arrest, aberrant mitosis, and cell death. CDK4/6i (palbociclib, ribociclib, abemaciclib) are relatively new cell cycle inhibitors that have been found to be effective in breast cancer treatment, and are currently being developed in other solid tumors. CDK4/6i blocks cell cycle progression at the G1 phase, resulting in cell death by mechanisms not yet fully elucidated. At first glance, paclitaxel and CDK4/6i are unlikely synergistic agents as both are cell cycle inhibitors that work at different phases of the cell cycle, and few clinical trials have yet considered adding CDK4/6i to existing paclitaxel chemotherapy. However, recent findings suggest the importance of a non-mitotic mechanism of paclitaxel in cancer cell death and pre-clinical data support rationale for a strategic paclitaxel and CDK4/6i combination. In mouse tumor model studies, drug sequencing resulted in differential efficacy, indicating complex biological interactions of the two drugs. This article reviews the rationales of combining paclitaxel with CDK4/6i as a potential therapeutic option in recurrent ovarian cancer.

Racial disparities in breast cancer preclinical and clinical models.

Breast cancer (BCa) has long been a health burden to women across the globe. However, the burden is not equally carried across races. Though the manifestation and behavior of BCa differs among racial groups, the racial representation of models used in preclinical trials and clinical trial participants lacks this heterogeneity. Women of African Ancestry (WAA) are disproportionately afflicted by having an increased risk of developing BCas that are more aggressive in nature, and consequently suffer from poorer outcomes relative to women of European ancestry (WEA). Notwithstanding this, one of the most commonly used tools in studying BCa, cell lines, exhibit a sizeable gap in cell line derivatives of WEA relative to WAA. In this review, we summarize the available BCa cell lines grouped by race by major suppliers, American Type Culture Collection (ATCC) and the European Collection of Authenticated Cell Cultures (ECACC). Next, examined the enrollment of WAA in clinical trials for BCa. Of the cell lines found provided by ATCC and ECACC, those derived from WEA constituted approximately 80% and 94%, respectively. The disparity is mirrored in clinical trial enrollment where, on average, WEA made up more than 70% of participants in trials found where ancestry information was provided. As both experimental models and clinical trial participants primarily consist of WEA, results may have poorer translatability toward other races. This highlights the need for greater racial diversity at the preclinical and clinical levels to more accurately represent the population and strengthen the translatability of results.

The vaginal microbiome is associated with endometrial cancer grade and histology.

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and ß diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and ß-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.

Impact of Federal, State, and Local Housing Policies on Disparities in Cardiovascular Disease in Black/African American Men and Women: From Policy to Pathways to Biology.

Racist and discriminatory federal, state, and local housing policies significantly contribute to disparities in cardiovascular disease incidence and mortality for individuals that self-identify as Black or African American. Here we highlight three key housing policies - "redlining," zoning, and the construction of highways - which have wrought a powerful, sustained, and destructive impact on cardiovascular health in Black/African American communities. Redlining and highway construction policies have restricted access to quality health care, increased exposure to carcinogens such as PM2.5, and increased exposure to extreme heat. At the root of these policy decisions are longstanding, toxic societal factors including racism, segregation, and discrimination, which also serve to perpetuate racial inequities in cardiovascular health. Here, we review these societal and structural factors and then link them with biological processes such as telomere shortening, allostatic load, oxidative stress, and tissue inflammation. Lastly, we focus on the impact of inflammation on the immune system and the molecular mechanisms by which the inflamed immune microenvironment promotes the formation of atherosclerotic plaques. We propose that racial residential segregation and discrimination increases tissue inflammation and cytokine production, resulting in dysregulated immune signaling, which promotes plaque formation and cardiovascular disease. This framework has the power to link structural racism not only to cardiovascular disease, but also to cancer.

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2.

Besides BRCA1 and BRCA2, several other inheritable mutations have been identified that increase ovarian cancer risk. Surgical excision of the fallopian tubes and ovaries reduces ovarian cancer risk, but for some non-BRCA hereditary ovarian cancer mutations the benefit of this intervention is unclear. The fallopian tubes of women with hereditary ovarian cancer mutations provide many insights into the early events of carcinogenesis and process of malignant transformation. Here we review cancer pathogenesis in hereditary cases of ovarian cancer, the occurrence of pre-invasive lesions and occult carcinoma in mutation carriers and their clinical management.

The DNA damage repair landscape in Black women with breast cancer.

BACKGROUND: Estrogen receptor positive (ER+) breast cancer is one of the most commonly diagnosed malignancies in women irrespective of their race or ethnicity. While Black women with ER+ breast cancer are 42% more likely to die of their disease than White women, molecular mechanisms underlying this disparate outcome are understudied. Recent studies identify DNA damage repair (DDR) genes as a new class of endocrine therapy resistance driver that contributes to poor survival among ER+ breast cancer patients. Here, we systematically analyze DDR regulation in the tumors and normal breast of Black women and its impact on survival outcome. METHOD: Mutation and up/downregulation of 104 DDR genes in breast tumor and normal samples from Black patients relative to White counterparts was assessed. For DDR genes that were differently regulated in the tumor samples from Black women in multiple datasets associations with survival outcome were tested. RESULTS: Overall, Black patient tumors upregulate or downregulate RNA levels of a wide array of single strand break repair (SSBR) genes relative to their white counterparts and uniformly upregulate double strand break repair (DSBR) genes. This DSBR upregulation was also detectable in samples of normal breast tissue from Black women. Eight candidate DDR genes were reproducibly differently regulated in tumors from Black women and associated with poor survival. A unique DDR signature comprised of simultaneous upregulation of homologous recombination gene expression and downregulation of SSBR genes was enriched in Black patients. This signature associated with cell cycle dysregulation (p < 0.001), a hallmark of endocrine therapy resistance, and concordantly, with significantly worse survival outcomes in all datasets analyzed (hazard ratio of 9.5, p < 0.001). CONCLUSION: These results constitute the first systematic analysis of DDR regulation in Black women and provide strong rationale for refining biomarker profiles to ensure precision medicine for underserved populations.

Altered Sleep Duration and Poor Quality of Sleep Among Pharmacy Students Amidst COVID-19 Lockdown: A South-Indian Study.

Introduction/background: The nationwide lockdown enforced due to the spread of coronavirus disease-2019 had a definite impact on sleep. Objective: To observe any changes in the duration, pattern and quality of sleep among pharmacy students due to the lockdown. Methods: A google form-based cross-sectional and descriptive study was carried out after approval was obtained from the ethical committee in the month of July 2021 among 310 pharmacy students. The validated form was electronically administered after obtaining the informed consent. All the data pertaining to duration, pattern and quality of sleep before and during the lockdown was collected and analyzed using STATA version 16.0. Results and Discussion: Out of 310 participants, the study revealed an increase in the time needed to fall asleep (p value < 0.001) and in the total duration of sleep (p value < 0.001). A delay in the time of sleep in the morning (p value < 0.001) and at night (p value < 0.001) was also one among the many significant results. The incidences of jerky leg movements (p value < 0.001), snoring (p value < 0.001), frequent nightmares (p value < 0.001) and anxiety (p value < 0.001) were also increased as a direct effect of the lockdown. Conclusion: The study has confirmed the detrimental impact of the lockdown on sleep among pharmacy students. All attributes of sleep duration and sleep quality have achieved statistical significance signifying the need to develop cognitive behavioral interventions and prevent the worsening of mental health amidst the COVID-19 era.

An Assessment of Ovarian Cancer Histotypes Across the African Diaspora.

OBJECTIVE: Ovarian cancer in Black women is common in many West African countries but is relatively rare in North America. Black women have worse survival outcomes when compared to White women. Ovarian cancer histotype, diagnosis, and age at presentation are known prognostic factors for outcome. We sought to conduct a preliminary comparative assessment of these factors across the African diaspora. METHODS: Patients diagnosed with ovarian cancer (all histologies) between June 2016-December 2019 in Departments of Pathology at 25 participating sites in Nigeria were identified. Comparative population-based data, inclusive of Caribbean-born Blacks (CBB) and US-born Blacks (USB), were additionally captured from the International Agency for Research on Cancer and Florida Cancer Data Systems. Histology, country of birth, and age at diagnosis data were collected and evaluated across the three subgroups: USB, CBB and Nigerians. Statistical analyses were done using chi-square and student's t-test with significance set at p<0.05. RESULTS: Nigerians had the highest proportion of germ cell tumor (GCT, 11.5%) and sex-cord stromal (SCST, 16.2%) ovarian cancers relative to CBB and USB (p=0.001). CBB (79.4%) and USB (77.3%) women were diagnosed with a larger proportion of serous ovarian cancer than Nigerians (60.4%) (p<0.0001). Nigerians were diagnosed with epithelial ovarian cancers at the youngest age (51.7± 12.8 years) relative to USB (58.9 ± 15.0) and CBB (59.0± 13.0,p<0.001). Black women [CBB (25.2 ± 15.0), Nigerians (29.5 ± 15.1), and USB (33.9 ± 17.9)] were diagnosed with GCT younger than White women (35.4 ± 20.5, p=0.011). Black women [Nigerians (47.5 ± 15.9), USB (50.9 ± 18.3) and CBB (50.9 ± 18.3)] were also diagnosed with SCST younger than White women (55.6 ± 16.5, p<0.01). CONCLUSION: There is significant variation in age of diagnosis and distribution of ovarian cancer histotype/diagnosis across the African diaspora. The etiology of these findings requires further investigation.

Magnifying the importance of collecting race, ethnicity, industry, and occupation data during the COVID-19 pandemic.

The contagiousness of coronavirus disease-2019 (COVID-19) led to the imposition of historical lockdowns in various countries. No scientific mind could have made accurate projections of the tremendous impact that COVID-19 would have on nations, communities, and the global-wide economy. Meanwhile, millions of workers have lost their jobs, while healthcare workers are overwhelmed and are reaching a state of mental and physical exhaustion. With the uncontrollable spread, researchers have been working to identify factors associated with COVID-19. In this regard, race, ethnicity, industry, and occupation have been found to be predominant factors of interest. However, unfortunately, the unavailability of such information has been a difficult reality. Since race, ethnicity, and employment are essential social determinants of health and could serve as potential risk-factors for COVID-19, collecting such information may offer important context for prioritising vulnerable groups. Thus, this perspective aims to highlight the importance and need for collecting race, ethnicity, and occupation-related data to track and treat the racial/ethnic groups that have been most strongly affected by the COVID-19 pandemic. Collecting such data will provide valuable insights and help public health officials recognise workplace-related outbreaks and evaluate the odds of various ethnic groups and professions contracting COVID-19.

Was Sleep a Problem for the Elderly During COVID-19?

Over the past few decades, the population of geriatrics has seen an exponential rise and it is well known that the prevalence of chronic diseases and other associated comorbidities is higher among them which in turn, has an established association with sleep disorders. During these unprecedented circumstances, geriatrics are predisposed to be at an increased risk of sleep disorders due to the social isolation and loneliness imposed on them by the lockdowns. The fact that older adults are at a greater risk of contracting the virus due to the presence of comorbidities and the high virulence adds on to the existing risk of sleep disturbances. A lack of sleep in these circumstances has the potential to add on to the vicious cycle of sleep disorders predisposed by chronic disease and vice versa. Mental health, sleep and the presence of comorbidities are closely interlinked and they often tend to overlap. Research in sleep has established insomnia to be the most commonly diagnosed sleep disorder affecting almost 50% of the older adults which can subsequently, elevate their risk of falls. This prevalence of sleep disorders is hypothesized to increase during the second wave of the COVID-19 pandemic and a good sleep routine needs to be advocated for to improve the quality of life of this population. However, scientific evidence concerning this is scarce and this review aims to highlight the significance of sleep and urges its readers to undertake studies that investigate the architecture of sleep amongst older adults during the pandemic.

Human Papilloma Virus Distribution Across the African Diaspora.

PURPOSE: Understanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora. METHODS: This study was approved by the African Caribbean Consortium (AC3). Six member institutions (Benin, Ethiopia, The Bahamas, Tobago, Curacao, and Jamaica) provided independently collected HPV data. Prevalence comparisons across for each nation were performed followed by an assessment of anticipated 9-valent vaccine coverage. Chi-square or Fisher's exact tests were used with significance at P < .05. RESULTS: One thousand three hundred fifty high-risk (HR) and 584 low-risk (LR) HPV subtypes were identified in the entire cohort. The most common HR HPV subtype was HPV 16 (17.9%) of infections. The distribution of HR and LR subtypes varied by country. The proportion of HR-HPV subtypes covered by the current 9-valent vaccine was lower in African countries compared with the Caribbean countries (47.9% v 67.9%; P < .01). No significant difference was seen for LR subtypes (8.1% African continent v 5.2% Caribbean; P = .20). Marked variation in the proportion of infections covered by the 9-valent vaccine persisted in individual countries. CONCLUSION: Significant variations in HPV prevalence were identified among African and Afro-Caribbean women. A large number of women in these regions are potentially uncovered by current vaccination formulation, particularly low-risk HPV infections.