Prostate Cancer In African Men Research Articles

Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.

Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Anatomic Locations and Metastatic Risk in Prostate Cancer in African Men: Insights From an African Cohort.

There is significant variability in the pathogenetic characteristics of prostate cancer (PCa) across different anatomical zones. This study aims to understand the metastatic risk associated with these zonal predispositions among African men. This hospital-based retrospective observational study included 120 biopsy-confirmed PCa patients examined between 2019 and 2023. Data on cancer history, sociodemographic, and clinical characteristics were collected from medical records. A logistic regression model was used to identify predictors of metastasis. The majority of PCa lesions were found in the left (60.0%) and right peripheral zones (55.8%), followed by the left (42.5%) and right transitional zones (41.7%). Lesions in the anterior fibromuscular stroma (crude odds ratio (cOR): 3.27, 95% confidence interval (CI): 1.13-9.47; p = 0.029), central gland (cOR: 5.38, 95% CI: 1.40-20.60; p = 0.014), and diffuse infiltration involving whole gland (cOR: 6.78, 95% CI: 1.17-30.07; p = 0.032) were associated with significantly increased odds of metastasis. Lesions in the anterior fibromuscular stroma were a marginally independent predictor of metastasis (adjusted odds ratio (aOR): 28.14, 95% CI: 0.96-822.46; p = 0.053). This study underscores the variability in metastatic risk of PCa lesions across different anatomical zones in African men. Lesions in the anterior fibromuscular stroma, central gland, and diffuse infiltration involving the whole gland have higher odds of metastasis. These findings highlight the need for targeted diagnostic and therapeutic strategies based on lesion localization to improve PCa management in this population.

Comparison of Serum Microseminoprotein-Beta (MSMB) with Total Prostate Specific Antigen (TPSA) in the Diagnosis of Prostate Cancer in African Men

Comparison of Serum Microseminoprotein-Beta (MSMB) with Total Prostate Specific Antigen (TPSA) in the Diagnosis of Prostate Cancer in African Men

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. A direct study-matched comparison between African- and European-derived, treatment-naïve, high-risk prostate tumors for 15 cases allowed for further comparative analyses of existing data. Excluding a single hypermutated tumor with 55 mutations per megabase, we observed a 1.8-fold increase in small somatic variants in African- versus European-derived tumors (P = 1.02e-04), rising to 4-fold when compared with published tumor-matched data. Furthermore, we observed an increase in oncogenic driver mutations in African tumors (P = 2.92e-03); roughly 30% of impacted genes were novel to prostate cancer, and 79% of recurrent driver mutations appeared early in tumorigenesis. Although complex genomic rearrangements were less frequent in African tumors, we describe a uniquely hyperduplicated tumor affecting 149 transposable elements. Comparable with African Americans, ERG fusions and PIK3CA mutations were absent and PTEN loss less frequent. CCND1 and MYC were frequently gained, with somatic copy-number changes more likely to occur late in tumorigenesis. In addition to traditional prostate cancer gene pathways, genes regulating calcium ion-ATPase signal transduction were disrupted in African tumors. Although preliminary, our results suggest that further validation and investigation into the potential implications for elevated tumor mutational burden and tumor-initiating mutations in clinically unfavorable prostate cancer can improve patient outcomes in Africa. SIGNIFICANCE: The first whole-genome sequencing study for high-risk prostate cancer in African men allows a simultaneous comparison of ethnic differences relative to European populations and of the influences of the environment relative to African-American men. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/78/24/6736/F1.large.jpg.See related commentary by Huang, p. 6726.

Abstract LB-371: ERG protein expression in diagnostic prostate cancer tissues among West African men

Abstract Background: Fusion of androgen regulated TMPRSS2 gene and the ERG oncogene is a common recurrent chromosomal aberration in prostate cancer, which leads to elevated expression of ERG oncoprotein. ERG expression detected by immunohistochemistry (IHC) has been validated as a proxy of TMPRSS2-ERG gene fusion. The prevalence of TMPRSS2-ERG gene fusion has been shown to vary by race being highest in Caucasian prostate cancer patients, followed by African American and then Asian. However, the prevalence of TMPRSS2-ERG gene fusion in African prostate cancer populations remains to be determined. Methods and Materials: There were 428 prostate cancer patients diagnosed during 2004-2012 in the Ghana Prostate Study who had formalin-fixed paraffin-embedded needle biopsy tissues available for analysis. Pathologists centrally scored 262 tissue samples for ERG expression and Gleason patterns, after excluding 166 without sufficient tissues. ERG-positive nuclear immunostaining of normal endothelial cells was used as an internal control and only nuclear immunostaining of prostate cancer cells was deemed ERG-positive. We evaluated ERG expression status in relation to clinicopathological characteristics using logistic regression models. To assess potential selection bias, we performed sensitivity analyses comparing clinicopathological characteristics extracted from medical records by inclusion/exclusion status. Results: We found 47 (18%) tissue samples were ERG-positive. Since recently preserved tissues appeared more likely to be ERG-negative (P = 0.044), all logistic regression models were adjusted for calendar year of diagnosis. Negative ERG staining was significantly associated with higher Gleason score (P = 0.035), in particular with higher primary Gleason grade (P = 0.028). Age at diagnosis, PSA concentration at diagnosis, and tribal group were not significantly associated with ERG expression status. Sensitivity analyses revealed that excluded tissues were more likely to be preserved in earlier years (P = 0.033) and to have lower Gleason scores (P = 0.003). Conclusions: This first study of ERG expression in an African prostate cancer population indicates that the prevalence of TMPRSS2-ERG gene fusion is similar to that of African American patients but lower than those with European ancestry. Whether this lower proportion of TMPRSS2-ERG gene fusion leads to a greater proportion of aggressive prostate cancer in African men or is the result of diagnostic selection of a higher proportion of symptomatic, high Gleason score prostate cancers in such populations remains unknown. Citation Format: Cindy Ke Zhou, Denise Young, Edward D. Yeboah, Richard B. Biritwum, Andrew A. Adjei, Yao Tettey, Evelyn Tay, Shelley Niwa, Ann L. Truelove, Isabell A. Sesterhenn, Shiv Srivastava, Robert N. Hoover, Ann W. Hsing, Michael B. Cook. ERG protein expression in diagnostic prostate cancer tissues among West African men. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-371.

The feasibility of epidemiological research on prostate cancer in African men in Ibadan, Nigeria.

BackgroundMen of African descent have the highest incidence and mortality rates of prostate cancer (PrCa) worldwide. Notably, PrCa is increasing in Africa with Nigerian men being mostly affected. Thus, it is important to understand risk factors for PrCa in Nigeria and build capacity for cancer research. The goals of this study were to determine the feasibility of conducting an epidemiological study of PrCa and to obtain preliminary data on risk factors for PrCa in Nigeria.MethodsA case–control study (50 cases/50 controls) was conducted at the University College Hospital (UCH) in Ibadan, Nigeria, between October 2011 and December 2012. Men aged 40 to 80 years were approached for the study and asked to provide informed consent and complete the research protocol. Logistic regression models were used to examine associations between demographic, social and lifestyle characteristics and risk of PrCa.ResultsThe participation rate among cases and controls was 98% and 93%, respectively. All participants completed a questionnaire and 99% (50 cases/49 controls) provided blood samples. Cases had a median serum diagnostic PSA of 73 ng/ml, and 38% had a Gleason score 8–10 tumor. Family history of PrCa was associated with a 4.9-fold increased risk of PrCa (95% CI 1.0 - 24.8). There were statistically significant inverse associations between PrCa and height, weight and waist circumference, but there was no association with body mass index (kg/m2). There were no associations between other socio-demographic and lifestyle characteristics and PrCa risk.ConclusionThis feasibility study demonstrated the ability to ascertain and recruit participants at UCH and collect epidemiological, clinical and biospecimen data. Our results highlighted the advanced clinical characteristics of PrCa in Nigerian men, and that family history of PrCa and some anthropometric factors were associated with PrCa risk in this population. However, larger studies are needed to better understand the epidemiological risk factors of PrCa in Nigeria.

Abstract 2552: A genome-wide association study of prostate cancer in West African men.

Abstract Age-adjusted mortality rates for prostate cancer are higher for Africa compared with North America or Western Europe. In addition, African American men are noted to have higher age-adjusted incidence rates of this malignancy than European American men. Coupled with the fact that West Africa is the principal ancestral region of African-American men has led to the hypothesis that there may exist distinct ancestral genetic profiles which mediate prostate cancer risk. In addition, advantages of conducting a genome-wide association study (GWAS) of prostate cancer in African men include a more discrete linkage disequilibrium (LD) structure, a higher number of private single nucleotide polymorphisms (SNPs), the predominance of symptomatic disease, and assessment of unique exposures. The Ghana Prostate Study was conducted collaboratively involving the US National Cancer Institute (NCI) and the University of Ghana during 2006-2012. The NCI Cancer Genomics Research Laboratory genotyped 494 prostate cancer cases and 498 population controls using the Illumina HumanOmni5-Quad BeadChip. Associations were assessed using multivariate logistic regression adjusted for age and genetic ancestry. We sought to validate the 30 most promising SNP associations with prostate cancer through the African American Prostate Cancer GWAS Consortium. A novel locus at 10p14 for prostate cancer risk was the strongest signal detected, and the 8 SNPs at this locus were in LD. This locus is located 360 kb 5’ of GATA3 and the 8 SNPs reside within an intron of LincRNA gene RP11-543F8.2. Analysis of African 1000 Genomes Project data did not indicate LD between 10p14 SNPs and splice or exonic SNPs of this gene, while HaploReg found no significant enrichment of enhancer elements. None of the most promising 30 SNPs replicated in the African American Prostate Cancer GWAS Consortium. This may be due to chance or differences in population genetics, environment, and/or proportion of symptomatic disease. Further genetic studies of prostate cancer in African men are needed to validate the 10p14 susceptibility locus. Citation Format: Michael B. Cook, Zhaoming Wang, Edward D. Yeboah, Andrew A. Adjei, Yao Tettey, Richard B. Biritwum, Evelyn Tay, Ann Truelove, Shelley Niwa, Lisa Chu, Meredith Yeager, Amy Hutchinson, Kai Yu, Christopher A. Haiman, African American Prostate Cancer GWAS Consortium, Robert N. Hoover, Ann Hsing, Stephen J. Chanock. A genome-wide association study of prostate cancer in West African men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2552. doi:10.1158/1538-7445.AM2013-2552