Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease
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, theref...
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doaj-acfd8ad7212b42ae95ccb55b8c747e852021-02-13T00:00:59ZengMDPI AGCancers2072-66942021-02-011376076010.3390/cancers13040760Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive DiseaseEdward J. Saunders0Zsofia Kote-Jarai1Rosalind A. Eeles2Institute of Cancer Research, London SM2 5NG, UKInstitute of Cancer Research, London SM2 5NG, UKInstitute of Cancer Research, London SM2 5NG, UKProstate 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.https://www.mdpi.com/2072-6694/13/4/760prostate canceraggressive prostate cancerprostate cancer susceptibilityprostate cancer geneticsgenome-wide association studiesmassively parallel sequencing studies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Edward J. Saunders Zsofia Kote-Jarai Rosalind A. Eeles |
spellingShingle |
Edward J. Saunders Zsofia Kote-Jarai Rosalind A. Eeles Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease Cancers prostate cancer aggressive prostate cancer prostate cancer susceptibility prostate cancer genetics genome-wide association studies massively parallel sequencing studies |
author_facet |
Edward J. Saunders Zsofia Kote-Jarai Rosalind A. Eeles |
author_sort |
Edward J. Saunders |
title |
Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease |
title_short |
Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease |
title_full |
Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease |
title_fullStr |
Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease |
title_full_unstemmed |
Identification of Germline Genetic Variants That Increase Prostate Cancer Risk and Influence Development of Aggressive Disease |
title_sort |
identification of germline genetic variants that increase prostate cancer risk and influence development of aggressive disease |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-02-01 |
description |
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. |
topic |
prostate cancer aggressive prostate cancer prostate cancer susceptibility prostate cancer genetics genome-wide association studies massively parallel sequencing studies |
url |
https://www.mdpi.com/2072-6694/13/4/760 |
work_keys_str_mv |
AT edwardjsaunders identificationofgermlinegeneticvariantsthatincreaseprostatecancerriskandinfluencedevelopmentofaggressivedisease AT zsofiakotejarai identificationofgermlinegeneticvariantsthatincreaseprostatecancerriskandinfluencedevelopmentofaggressivedisease AT rosalindaeeles identificationofgermlinegeneticvariantsthatincreaseprostatecancerriskandinfluencedevelopmentofaggressivedisease |
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