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Why do African-American men face higher risks for lethal prostate cancer?

ABSTRACT:

Purpose of review

African-American men in the USA have a higher incidence of and mortality from prostate cancer (PCa), with a longstanding debate about the cause for these worse outcomes. This review examines differences in tumour biology and socioeconomics for African-American and Non-Hispanic White (NHW) men to answer the question 'why AA men face higher risks for lethal PCa' and draw a management consensus to redress the imbalance.

Recent findings

Recent evidence from over the past 2 years suggests the reasons why African-American men face a higher risk of lethal PCa are multifactorial, with contributions from differences in tumour biology as well as socioeconomic and healthcare access factors. Regarding tumour biology, genomic and transcriptome profiling suggests African-American men have upregulated expression of genes related to inflammatory pathways with downregulation of DNA repair genes. In contrast, NHW men have higher DNA repair pathways and metabolic pathways involving glycolysis and cell cycle activity. In addition, epidemiological evidence suggests equal healthcare access ensures equal PCa specific outcomes, implying African-American men's disease is not inherently more lethal. However, differences in tumour biology remain, which may explain specific differences in PCa incidence and the clinical findings of African-American men's increased response to immunotherapy and radiotherapy in recent trials.

Summary

Regardless of racial differences in disease outcomes and the factors causing them, African-American and NHW men seem to have diseases unique to their ancestry. This supports the exploration of personalized PCa treatment approaches, leveraging translational basic science research to uncover these differences and devise specific individualized methods therapeutic regimes to address them.

SUBMITTER: Nair SS

PROVIDER: S-EPMC8635247 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.