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Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease

1
The Institute of Cancer Research, London SM2 5NG, UK
2
Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Delila Gasi Tandefelt
Cancers 2021, 13(4), 760; https://doi.org/10.3390/cancers13040760
Received: 15 December 2020 / Revised: 8 February 2021 / Accepted: 9 February 2021 / Published: 12 February 2021
(This article belongs to the Special Issue Prostate Cancer—from Molecular Mechanisms to Clinical Care)
The potential importance of germline genetic variation for identifying men at increased risk of prostate cancer has become increasingly recognised in recent years. We present an extensive review of the major developments in the identification of genetic loci, genes and individual variants associated with greater risk of prostate cancer, and what is currently known regarding whether these heritable prostate cancer risk factors can also inform likelihood of experiencing clinically significant rather than indolent forms of the disease. We finally discuss how these research discoveries might serve to inform clinical germline genetic testing guidelines and treatment options for prostate cancer in the future.
Prostate cancer (PrCa) is a heterogeneous disease, which presents in individual patients across a diverse phenotypic spectrum ranging from indolent to fatal forms. No robust biomarkers are currently available to enable routine screening for PrCa or to distinguish clinically significant forms, therefore late stage identification of advanced disease and overdiagnosis plus overtreatment of insignificant disease both remain areas of concern in healthcare provision. PrCa has a substantial heritable component, and technological advances since the completion of the Human Genome Project have facilitated improved identification of inherited genetic factors influencing susceptibility to development of the disease within families and populations. These genetic markers hold promise to enable improved understanding of the biological mechanisms underpinning PrCa development, facilitate genetically informed PrCa screening programmes and guide appropriate treatment provision. However, insight remains largely lacking regarding many aspects of their manifestation; especially in relation to genes associated with aggressive phenotypes, risk factors in non-European populations and appropriate approaches to enable accurate stratification of higher and lower risk individuals. This review discusses the methodology used in the elucidation of genetic loci, genes and individual causal variants responsible for modulating PrCa susceptibility; the current state of understanding of the allelic spectrum contributing to PrCa risk; and prospective future translational applications of these discoveries in the developing eras of genomics and personalised medicine. View Full-Text
Keywords: prostate cancer; aggressive prostate cancer; prostate cancer susceptibility; prostate cancer genetics; genome-wide association studies; massively parallel sequencing studies prostate cancer; aggressive prostate cancer; prostate cancer susceptibility; prostate cancer genetics; genome-wide association studies; massively parallel sequencing studies
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MDPI and ACS Style

Saunders, E.J.; Kote-Jarai, Z.; Eeles, R.A. Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease. Cancers 2021, 13, 760. https://doi.org/10.3390/cancers13040760

AMA Style

Saunders EJ, Kote-Jarai Z, Eeles RA. Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease. Cancers. 2021; 13(4):760. https://doi.org/10.3390/cancers13040760

Chicago/Turabian Style

Saunders, Edward J.; Kote-Jarai, Zsofia; Eeles, Rosalind A. 2021. "Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease" Cancers 13, no. 4: 760. https://doi.org/10.3390/cancers13040760

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