Prostate Cancer Germline Variations and Implications for Screening and Treatment.
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Date
2018-09-04Author
Dias, A
Kote-Jarai, Z
Mikropoulos, C
Eeles, R
Type
Journal Article
Metadata
Show full item recordAbstract
Prostate cancer (PCa) is a highly heritable disease, and rapid evolution of sequencing technologies has enabled marked progression of our understanding of its genetic inheritance. A complex polygenic model that involves common low-penetrance susceptibility alleles causing individually small but cumulatively significant risk and rarer genetic variants causing greater risk represent the current most accepted model. Through genome-wide association studies, more than 100 single-nucleotide polymorphisms (SNPs) associated with PCa risk have been identified. Consistent reports have identified germline mutations in the genes BRCA1, BRCA2, MMR, HOXB13, CHEK2, and NBS1 as conferring moderate risks, with some leading to a more aggressive disease behavior. Considering this knowledge, several research strategies have been developed to determine whether targeted prostate screening using genetic information can overcome the limitations of population-based prostate-specific antigen (PSA) screening. Germline DNA-repair mutations are more frequent in men with metastatic disease than previously thought, and these patients have a more favorable response to therapy with poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors. Genomic information is a practical tool that has the potential to enable the concept of precision medicine to become a reality in all steps of PCa patient care.
Collections
Subject
Humans
Colorectal Neoplasms, Hereditary Nonpolyposis
Prostatic Neoplasms
Genetic Predisposition to Disease
Prostate-Specific Antigen
Ubiquitin-Protein Ligases
Cell Cycle Proteins
Homeodomain Proteins
BRCA2 Protein
Nuclear Proteins
DNA Repair
Germ-Line Mutation
Polymorphism, Single Nucleotide
Male
Early Detection of Cancer
Genome-Wide Association Study
Molecular Targeted Therapy
Checkpoint Kinase 2
Research team
Oncogenetics
Language
eng
Date accepted
2018-09-04
License start date
2018-09-04
Citation
Cold Spring Harbor perspectives in medicine, 2018, 8 (9)
Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
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