The Impact of African Ancestry on Prostate Cancer Disparities in the Era of Precision Medicine

Lewis, Deyana D.; Cropp, Cheryl D.

doi:10.3390/genes11121471

Cited by 24 publications

(17 citation statements)

References 250 publications

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“…Genetic variability contributes to the observed disparities in many diseases, including those with complex environmental and socio-economic determinants. For example, prostate cancer is the second most prevalent cancer diagnosis and the fifth most common cause of death in men worldwide; however, it disproportionately affects men of African ancestry [ 35 ]. Similarly, cardiovascular disease is a leading health problem worldwide, but its risk is governed by individual and population-scale variation in rare/Mendelian as well as common genomic regions [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent

Upadhyai

Suresh

Parit

et al. 2021

Life

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The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a wide spectrum of clinical phenotypes ranging from asymptomatic to symptomatic with mild or moderate presentation and severe disease. COVID-19 susceptibility, severity and recovery have demonstrated high variability worldwide. Variances in the host genetic architecture may underlie the inter-individual and population-scale differences in COVID-19 presentation. We performed a genome-wide association analysis employing the genotyping data from AncestryDNA for COVID-19 patients of European descent and used asymptomatic subjects as the control group. We identified 621 genetic variants that were significantly distinct between asymptomatic and acutely symptomatic COVID-19 patients (multiple-testing corrected p-value < 0.001). These variants were found to be associated with pathways governing host immunity, such as interferon, interleukin and cytokine signalling, and known COVID-19 comorbidities, such as obesity and cholesterol metabolism. Further, our ancestry analysis revealed that the asymptomatic COVID-19 patients possess discernibly higher proportions of the Ancestral North Eurasian (ANE) and Eastern Hunter-Gatherer (EHG) ancestry, which was introduced to Europe through Bell Beaker culture (Yamnaya related) and lower fractions of Western Hunter-Gatherer (WHG) ancestry, while severely symptomatic patients have higher fractions of WHG and lower ANE/EHG ancestral components, thereby delineating the likely ancestral differences between the two groups.

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Section: Discussionmentioning

confidence: 99%

Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent

Upadhyai

Suresh

Parit

et al. 2021

Life

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“…In 2020, the Global Cancer Observatory (GLOBOCAN) report noted an annual incidence of 1.4 million prostate cancer cases worldwide, with approximately 375,304 deaths [2]. Reports indicate that men of African ancestry suffer disproportionately from prostate cancer at a rate almost twice as high as men of European origin, irrespective of new treatment modalities [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Soluble Programmed Death-Ligand 1 (sPD-L1) is Elevated in Aggressive Prostate Cancer Disease Among African Men

et al. 2022

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Introduction: Programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men. Methods: Plasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined. Results: We found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014). Conclusions: Elevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy.

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“…For this reason, precision medicine is also known as personalized medicine. The application of precision medicine in cancer has proved to be a popular research goal and led to the adoption of the term precision oncology [ 2 , 3 ]. The customization of therapeutic regimens to each patient is important because of the unpredictable effects induced by therapeutic drugs that can vary from one person to another according to their own genetics, phenotypic, or psychosocial characteristics [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…While data are currently available on PCa in African men, there is still a lot we do not know about the role of the patient’s genome in the development and progression of PCa in African men [ 20 ]. Since African men have a poor PCa prognosis compared to their Caucasian counterparts, it is suspected that genetic differences resulting from different ancestry may play an important role in this difference (reviewed in [ 2 ]). PCa is not the only sex specific cancer where African populations have higher incidence and mortality rates.…”

Section: Introductionmentioning

confidence: 99%

Role of Precision Oncology in Type II Endometrial and Prostate Cancers in the African Population: Global Cancer Genomics Disparities

Marima

Hull

Mbeje

et al. 2022

IJMS

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Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.

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The Impact of African Ancestry on Prostate Cancer Disparities in the Era of Precision Medicine

Cited by 24 publications

References 250 publications

Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent

Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent

Soluble Programmed Death-Ligand 1 (sPD-L1) is Elevated in Aggressive Prostate Cancer Disease Among African Men

Role of Precision Oncology in Type II Endometrial and Prostate Cancers in the African Population: Global Cancer Genomics Disparities

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