Whole-exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways.

BACKGROUND: Through whole-exome sequencing of 60 formalin-fixed paraffin-embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non-European populations are lacking. METHODS: In this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH. RESULTS: Two hundred and two nonbenign, ClinVar-annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co-occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co-occurring interactions. Two hundred and seventy-nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11-595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair. CONCLUSIONS: NGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

Food insecurity among university students in the United States amidst the COVID-19 pandemic.

OBJECTIVE: This study reports on food insecurity (FI) amidst the COVID-19 pandemic. PARTICIPANTS AND METHODS: College students in four regions of the US completed the two-item validated Hunger Vital Sign™ screening tool on Qualtrics. RESULTS: FI increased significantly after March 2020 among US students (worry about food running out: 25% to 35%; food did not last: 17% to 21%) with significant regional increase in the Midwest and South. An adjusted multivariable logistic regression model indicated students that ran out of food were significantly at greater odds of experiencing hardship with paying bills (AOR: 5.59, 95% CI =3.90-8.06). CONCLUSIONS: The findings identified an increase in the prevalence of FI among college students during the pandemic. Suggestions of how to address FI are discussed.

Whole-exome Sequencing of Nigerian Prostate Tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) Reveals DNA Repair Genes Associated with African Ancestry.

In this study, we used whole-exome sequencing of a cohort of 45 advanced-stage, treatment-naïve Nigerian (NG) primary prostate cancer tumors and 11 unmatched nontumor tissues to compare genomic mutations with African American (AA) and European American (EA) The Cancer Genome Atlas (TCGA) prostate cancer. NG samples were collected from six sites in central and southwest Nigeria. After whole-exome sequencing, samples were processed using GATK best practices. BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2(18%) had germline alterations in at least two NG nontumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%), and PMS2 (16%)] similar to NG samples. Of the most frequently mutated genes, BRCA1 showed a statistically (P ≤ 0.05) higher germline mutation frequency in men of African ancestry (MAA) and increasing variant frequency with increased African ancestry. Disaggregating gene-level mutation frequencies by variants revealed both ancestry-linked and NG-specific germline variant patterns. Driven by rs799917 (T>C), BRCA1 showed an increasing mutation frequency as African ancestry increased. BRCA2_rs11571831 was present only in MAA, and BRCA2_rs766173 was elevated in NG men. A total of 133 somatic variants were present in 26 prostate cancer-associated genes within the NG tumor cohort. BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%), and PMS2 (11%) showed mutation frequencies >10%. Compared with TCGA cohorts, NG tumors showed statistically significant elevated frequencies of BRCA2, APC, and BRCA1. The NG cohort variant pattern shared similarities (cosign similarities ≥0.734) with Catalogue of Somatic Mutations in Cancer signatures 5 and 6, and mutated genes showed significant (q < 0.001) gene ontology (GO) and functional enrichment in mismatch repair and non-homologous repair deficiency pathways. Here, we showed that mutations in DNA damage response genes were higher in NG prostate cancer samples and that a portion of those mutations correlate with African ancestry. Moreover, we identified variants of unknown significance that may contribute to population-specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the NG prostate cancer exome to date and highlight the need to increase diversity of study populations. Significance: MAA have higher rates of prostate cancer incidence and mortality, however, are severely underrepresented in genomic studies. This is the first study utilizing whole-exome sequencing in NG men to identify West African ancestry-linked variant patterns that impact DNA damage repair pathways.

Improving Representation of Underrepresented Minority (URM) Students in Oncology Biomedical Research Workforce: Outcome Evaluation from the ReTOOL Program.

The Research Training Opportunities for Outstanding Leaders (ReTOOL) program was implemented in 2012 to increase the representation of racial and ethnic minorities in the biomedical workforce. Specifically, the ReTOOL program aims to foster the capacity for scientific research among underserved populations as well as address the cultural appropriateness of research projects. This paper describes the impact of the ReTOOL program in enhancing the research training of underrepresented minority (URM) students. Forty URM students who completed the ReTOOL program between 2012 and 2019 were invited to participate in the program evaluation. The response rate was 73% with 29 participants. Of the 29 participants, 26 trainees self-identified as Black or African-American. A structured survey developed for the program was employed for data collection, using a Likert Scale ranging from 1 to 5, with 5 being the best. The item ratings ranged from 4.45 to 4.80. Responses to open-ended questions show that ReTOOL has been instrumental in socializing and acculturating participants into the habits of scientific thinking. The combined use of quantitative and qualitative inquiry depicts that ReTOOL has been highly successful in fostering participant enrollment in advanced health-related or professional degree programs.

Development of a Minority Prostate Cancer Research Digest: Communication Strategy Statement for Black Men.

Since prostate cancer incidence, prevalence and mortality are still highest among Black men in the United States, it is important to effectively address the factors that contribute to prostate cancer disparities in this at-risk population as well as their low participation in biomedical research/clinical trials. An effective communication strategy that can be used to disseminate information with high public health impact to Black men is one way to combat prostate cancer disparities. The objective of this study was to develop a Minority Prostate Cancer (MiCaP) research communication strategy using focus group methodology and expert in-depth interviews. The communication strategy statement developed in this study provides a guide for message concepts and materials for Black men, including communication content, source, channel, and location. Specifically, it provides recommendations on how to deliver information, how to choose the language and relevant images, how to gain attention, who is preferred to deliver messages, and other ways to engage Black men in health communication strategies. The communication strategy statement was used to develop the MiCaP Research Digest, a research communication program that is currently being tested in Orange County, Duval County, Leon County, Gadsden County, and the Tampa Bay area of Florida.

PSYCHOSOCIAL IMPACT OF COVID-19 ON STUDENTS AT INSTITUTIONS OF HIGHER LEARNING.

Students at higher institutions of learning are more susceptible to psychosocial problems compared to the general public. These may further be exacerbated by the measures put in place to curb the spread of COVID-19. This mixed methods study examined the factors associated with the psychosocial impact of COVID-19 on students' financial stability, interpersonal relationships and worries related to achieving academic milestones. Data comprised of a series of closed and open-ended questions collected via Qualtrics from students in the United States and Africa (Central and West). The quantitative data were analyzed using frequency counts, percentages and chi-square, while the qualitative data was analyzed using thematic content analysis. More than 90% of the students resided in the United States, 72.5% were females and 78.4% were undergraduates. Financial hardship was experienced by 26.4% of the students, 55.8% indicated that COVID-19 negatively affected their relationship with friends and over 40% worried over delays in achieving academic milestones. Continent of residence, employment status and financial hardship were significantly associated with the negative impact of COVID-19 on one or more of the students' relationships and with worries about achieving academic milestones. Qualitative data support the findings that financial hardship contributed to experience of psychological distress by students. It also revealed negative (compromised relationships - broken or fractured relationships and loneliness) and positive (bonding) impact of COVID-19 on interpersonal relationships. School administrators should provide students with resources to access economic relief packages and tele-counseling services to help meet their financial and psychosocial support needs amidst COVID-19.

Pathology Services in Nigeria: Cross-Sectional Survey Results From Three Cancer Consortia.

PURPOSE: Cancer incidence is increasing in sub-Saharan Africa, yet there is little information on the capacity of pathology laboratories in this region. We aimed to assess the current state of pathology services in Nigeria to guide strategies to ensure best practices and improve the quality of surgical specimen handling. METHODS: We developed structured pathology survey to assess tissue handling, sample processing, and immunohistochemistry (IHC) capabilities. The survey was distributed electronically to 22 medical centers in Nigeria that are part of established cancer consortia. Data were collected between September and October 2017. RESULTS: Sixteen of 22 centers completed the survey in full. All 16 institutions had at least one board-certified pathologist and at least one full-time laboratory scientist/technologist. The majority of responding institutions (75%) reported processing fewer than 3,000 samples per year. For sample processing, 38% of institutions reported manual tissue processing and 75% processed biopsies and surgical specimens together. The average tissue fixation time ranged from 5 to more than 72 hours before processing and paraffin embedding. Half of the institutions reported having no quality assurance processes to evaluate hematoxylin and eosin-stained slides, and 25% reported having no written operating procedures. Half of the participating institutions have a facility for routine IHC staining, and among these there was considerable variability in processes and validation procedures. External proficiency testing was not common among surveyed sites (38%). CONCLUSION: Data from 16 Nigerian medical institutions indicate deficiencies in standardization, quality control, and IHC validation that could affect the reliability of pathology results. These findings highlight addressable gaps in pathology services that can ensure accurate diagnosis and follow-up for the growing number of patients with cancer in this region.

Choosing Channels, Sources, and Content for Communicating Prostate Cancer Information to Black Men: A Systematic Review of the Literature.

The purpose of this study was to identify effective channels, sources, and content approaches for communicating prostate cancer prevention information to Black men. The Web of Science, PubMed and GoogleScholar databases, as well as reviews of reference lists for selected publications, were searched to select articles relevant to cancer communication channels, sources or content for Black men, focused on male-prevalent cancers and published in English. Articles were excluded if they examined only patient-provider communication, dealt exclusively with prostate cancer patients or did not separate findings by race. The selection procedures identified 41 relevant articles, which were systematically and independently reviewed by two team members to extract data on preferred channels, sources, and content for prostate cancer information. This review revealed that Black men prefer interpersonal communication for prostate cancer information; however, video can be effective. Trusted sources included personal physicians, clergy, and other community leaders, family (especially spouses) and prostate cancer survivors. Men want comprehensive information about screening, symptoms, treatment, and outcomes. Messages should be culturally tailored, encouraging empowerment and "ownership" of disease. Black men are open to prostate cancer prevention information through mediated channels when contextualized within spiritual/cultural beliefs and delivered by trusted sources.

Prostate Cancer Screening Perception, Beliefs, and Practices Among Men in Bamenda, Cameroon.

Prostate Cancer (CaP) is the most commonly diagnosed cancer among Cameroonian men. Due to inadequate infrastructure, record keeping, and resources, little is known about its true burden on the population. There are rural/urban disparities with regards to awareness, screening, treatment, and survivorship. Furthermore, use of traditional medicine and homeopathic remedies is widespread, and some men delay seeking conventional medical treatment until advanced stages of CaP. This study examined the perceptions, beliefs, and practices of men in Cameroon regarding late stage CaP diagnoses; identified factors that influence screening decision; and ascertained how men decided between traditional or conventional medicine for CaP diagnosis and treatment. Semistructured focus groups were used to collect data from men in Bamenda, Cameroon. Qualitative data analysis was used to analyze transcripts for emerging themes and constructs using a socio-ecological framework. Twenty-five men participated in the study, with an average age of 59. Most of the participants had never received a prostate screening recommendation. Socioeconomic status, local beliefs, knowledge levels, awareness of CaP and screening methods, and stigma were prominent themes. A significant number of Cameroonian men receive late stage CaP diagnosis due to lack of awareness, attitudes, cultural beliefs, self-medication, and economic limitation. To effectively address these contributing factors to late stage CaP diagnosis, a contextually based health education program is warranted and should be tailored to fill knowledge gaps about the disease, dispel misconceptions, and focus on reducing barriers to utilization of health services.