Genetic predisposition to prostate cancer.
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Date
2016-12-01Author
Benafif, S
Eeles, R
Type
Journal Article
Metadata
Show full item recordAbstract
INTRODUCTION: Prostate cancer (PrCa) is the commonest non-cutaneous cancer in men in the UK. Epidemiological evidence as well as twin studies points towards a genetic component contributing to aetiology. SOURCES OF DATA: Key recently published literature. AREAS OF AGREEMENT: A family history of PrCa doubles the risk of disease development in first-degree relatives. Linkage and genetic sequencing studies identified rare moderate-high-risk gene loci, which predispose to PrCa development when altered by mutation. Genome-wide association studies have identified common single-nucleotide polypmorphisms (SNPs), which confer a cumulative risk of PrCa development with increasing number of risk alleles. There are emerging data that castrate-resistant disease is associated with mutations in DNA repair genes. AREAS OF CONTROVERSY: Linkage studies investigating possible high-risk loci leading to PrCa development identified possible loci on several chromosomes, but most have not been consistently replicated by subsequent studies. Germline SNPs related to prostate specific antigen (PSA) levels and to normal tissue radiosensitivity have also been identified though not all have been validated in subsequent studies. GROWING POINTS: Utilizing germline SNP profiles as well as identifying high-risk genetic variants could target screening to high-risk groups, avoiding the drawbacks of PSA screening. AREAS TIMELY FOR DEVELOPING RESEARCH: Incorporating genetics into PrCa screening is being investigated currently using both common SNP profiles and higher risk rare variants. Knowledge of germline genetic defects will allow the development of targeted screening programs, preventive strategies and the personalized treatment of PrCa.
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Subject
Humans
Prostatic Neoplasms
Genetic Predisposition to Disease
Prostate-Specific Antigen
Reproducibility of Results
Germ-Line Mutation
Polymorphism, Single Nucleotide
Male
Early Detection of Cancer
Genome-Wide Association Study
United Kingdom
Research team
Oncogenetics
Language
eng
Date accepted
2016-09-04
License start date
2016-12
Citation
British medical bulletin, 2016, 120 (1), pp. 75 - 89
Publisher
OXFORD UNIV PRESS