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Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities

Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Rockville, MD 20852, USA
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Int. J. Mol. Sci. 2018, 19(4), 1255; https://doi.org/10.3390/ijms19041255
Received: 9 April 2018 / Revised: 15 April 2018 / Accepted: 15 April 2018 / Published: 22 April 2018
(This article belongs to the Special Issue Molecular Research on Urology)
Prostate cancer (CaP) is the most commonly diagnosed non-cutaneous cancer and the second leading cause of male cancer deaths in the United States. Among African American (AA) men, CaP is the most prevalent malignancy, with disproportionately higher incidence and mortality rates. Even after discounting the influence of socioeconomic factors, the effect of molecular and genetic factors on racial disparity of CaP is evident. Earlier studies on the molecular basis for CaP disparity have focused on the influence of heritable mutations and single-nucleotide polymorphisms (SNPs). Most CaP susceptibility alleles identified based on genome-wide association studies (GWAS) were common, low-penetrance variants. Germline CaP-associated mutations that are highly penetrant, such as those found in HOXB13 and BRCA2, are usually rare. More recently, genomic studies enabled by Next-Gen Sequencing (NGS) technologies have focused on the identification of somatic mutations that contribute to CaP tumorigenesis. These studies confirmed the high prevalence of ERG gene fusions and PTEN deletions among Caucasian Americans and identified novel somatic alterations in SPOP and FOXA1 genes in early stages of CaP. Individuals with African ancestry and other minorities are often underrepresented in these large-scale genomic studies, which are performed primarily using tumors from men of European ancestry. The insufficient number of specimens from AA men and other minority populations, together with the heterogeneity in the molecular etiology of CaP across populations, challenge the generalizability of findings from these projects. Efforts to close this gap by sequencing larger numbers of tumor specimens from more diverse populations, although still at an early stage, have discovered distinct genomic alterations. These research findings can have a direct impact on the diagnosis of CaP, the stratification of patients for treatment, and can help to address the disparity in incidence and mortality of CaP. This review examines the progress of understanding in CaP genetics and genomics and highlight the need to increase the representation from minority populations. View Full-Text
Keywords: prostate cancer; cancer genomics; hereditary prostate cancer; cancer health disparities prostate cancer; cancer genomics; hereditary prostate cancer; cancer health disparities
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Tan, S.-H.; Petrovics, G.; Srivastava, S. Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities. Int. J. Mol. Sci. 2018, 19, 1255.

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