The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities.

The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability.

Prostate cancer genetic risk and associated aggressive disease in men of African ancestry.

African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men.

ANO7 African-ancestral genomic diversity and advanced prostate cancer.

Background: Prostate cancer (PCa) is a significant health burden for African men, with mortality rates more than double global averages. The prostate specific Anoctamin 7 (ANO7) gene linked with poor patient outcomes has recently been identified as the target for an African-specific protein-truncating PCa-risk allele.

Methods: Here we determined the role of ANO7 in a study of 889 men from southern Africa, leveraging exomic genotyping array PCa case-control data (n = 780, 17 ANO7 alleles) and deep sequenced whole genome data for germline and tumour ANO7 interrogation (n = 109), while providing clinicopathologically matched European-derived sequence data comparative analyses (n = 57).

Alterations in the Epigenetic Machinery Associated with Prostate Cancer Health Disparities.

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry as a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Investigating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found that African-derived tumors present with a longer tail of epigenetic driver gene candidates (72 versus 10).

Evaluating Germline Testing Panels in Southern African Males With Advanced Prostate Cancer.

Background: Germline testing for prostate cancer is on the increase, with clinical implications for risk assessment, treatment, and management. Regardless of family history, NCCN recommends germline testing for patients with metastatic, regional, very-high-risk localized, and high-risk localized prostate cancer. Although African ancestry is a significant risk factor for aggressive prostate cancer, due to a lack of available data no testing criteria have been established for ethnic minorities.

Social acceptance of livestock-administered endectocides for malaria control in Vhembe District, Limpopo Province, South Africa.

Background: Malaria continues to be a leading cause of morbidity and mortality in Africa and conventional malaria control strategies, such as indoor residual spraying and insecticide-treated bed nets, have limited effectiveness for some malarial vectors. Consequently, the development of alternative or supplementary strategies is required. One potential strategy is the use of livestock-administered endectocides to control vector mosquitoes that feed outdoors on livestock.

African-specific molecular taxonomy of prostate cancer.

Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages.

EDCs and male urogenital cancers.

Male sex determination and sexual differentiation occur between 6-12 weeks of gestation. During the "male programming window" the fetal testes start to produce testosterone that initiates the development of the male reproductive tract. Exposure to endocrine disrupting chemicals (EDCs) able to mimic or disrupt steroid hormone actions may disrupt testicular development and adversely impact reproductive health at birth, during puberty and adulthood.

DNA methylation profiles unique to Kalahari KhoeSan individuals.

Genomes of KhoeSan individuals of the Kalahari Desert provide the greatest understanding of single nucleotide diversity in the human genome. Compared with individuals in industrialized environments, the KhoeSan have a unique foraging and hunting lifestyle. Given these dramatic environmental differences, and the responsiveness of the methylome to environmental exposures of many types, we hypothesized that DNA methylation patterns would differ between KhoeSan and neighbouring agropastoral and/or industrial Bantu.

MethylToSNP: identifying SNPs in Illumina DNA methylation array data.

Background: Current array-based methods for the measurement of DNA methylation rely on the process of sodium bisulfite conversion to differentiate between methylated and unmethylated cytosine bases in DNA. In the absence of genotype data this process can lead to ambiguity in data interpretation when a sample has polymorphisms at a methylation probe site. A common way to minimize this problem is to exclude such potentially problematic sites, with some methods removing as much as 60% of array probes from consideration before data analysis.

Metagenomic analysis reveals a rich bacterial content in high-risk prostate tumors from African men.

Background: Inflammation is a hallmark of prostate cancer (PCa), yet no pathogenic agent has been identified. Men from Africa are at increased risk for both aggressive prostate disease and infection. We hypothesize that pathogenic microbes may be contributing, at least in part, to high-risk PCa presentation within Africa and in turn the observed ethnic disparity.

TMPRSS2-ERG fusions linked to prostate cancer racial health disparities: A focus on Africa.

Background: The androgen-regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2-ERG. Data for Africa is scarce.

Extended High-Frequency Smartphone Audiometry: Validity and Reliability.

Background: Extended high-frequency (EHF) audiometry (8-16 kHz) has an important role in audiological assessments such as ototoxicity monitoring, and for speech recognition and localization. Accurate and reliable EHF testing with smartphone technologies has the potential to provide more affordable and accessible hearing-care services, especially in underserved contexts.

Purpose: To determine the accuracy and test-retest reliability of EHF audiometry with a smartphone application, using calibrated headphones.

Whole-Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer.

: African-American men are more likely than any other racial group to die from prostate cancer. The contribution of acquired genomic variation to this racial disparity is largely unknown, as genomic from Africa is lacking. Here, we performed the first tumor-normal paired deep whole-genome sequencing for Africa.

Alterations in male reproductive hormones in relation to environmental DDT exposure.

DDT [1, 1, 1-trichloro-2,2-bis (p-chlorophenyl)-ethane] compounds are used for indoor residual spraying (IRS) to control malaria mosquitoes. DDT is an endocrine disruptor chemical in experimental conditions, but little is known of adverse effects related to living conditions with continual uptake across a time span by all possible means of exposure. Based on estrogenic and/or anti-androgenic effects found in animal studies, we hypothesized that chronic DDT/DDE exposures in men may be associated with changes in male reproductive hormones.

Interactive Malaria Education Intervention and Its Effect on Community Participant Knowledge: The Malaria Awareness Program in Vhembe District, Limpopo, South Africa.

Malaria is preventable and treatable, yet remains the most prevalent parasitic endemic disease in Africa. This article analyzes prospective observational data from the Malaria Awareness Program (MAP), an interactive malaria education initiative led by home-based care workers to improve participant knowledge of malaria as a precursor to increased uptake of malaria control interventions in the Vhembe District, Limpopo, South Africa. Between 2012 and 2016, 1,330 individuals participated in MAP.

Endocrine Disruptors and Health Effects in Africa: A Call for Action.

Background: Africa faces a number of unique environmental challenges. Unfortunately, it lacks the infrastructure needed to support the comprehensive environmental studies that could provide the scientific basis to inform environmental policies. There are a number of known sources of endocrine-disrupting chemicals (EDCs) and other hazardous chemicals in Africa.

Next generation mapping reveals novel large genomic rearrangements in prostate cancer.

Complex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies.