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Prostate Cancer Germline Variations and Implications for Screening and Treatment.

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Accepted version (811.2Kb)
Date
2018-09-04
ICR Author
Eeles, Rosalind
Kote-Jarai, Zsofia
Author
Dias, A
Kote-Jarai, Z
Mikropoulos, C
Eeles, R
Type
Journal Article
Metadata
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Abstract
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.
URI
https://repository.icr.ac.uk/handle/internal/3180
DOI
https://doi.org/10.1101/cshperspect.a030379
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
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)

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