Translating Genetic Risk Factors for Prostate Cancer to the Clinic: 2013 and Beyond

Abstract

Prostate cancer (PrCa) is the most commonly diagnosed cancer in the male UK population, with over 40,000 new cases per year. PrCa has a complex, polygenic predisposition, due to rare variants such as BRCA and common variants such as single nucleotide polymorphisms (SNPs). With the introduction of genome-wide association studies, 78 susceptibility loci (SNPs) associated with PrCa risk have been identified. Genetic profiling could risk-stratify a population, leading to the discovery of a higher proportion of clinically significant disease and a reduction in the morbidity related to age-based prostate-specific antigen screening. Based on the combined risk of the 78 SNPs identified so far, the top 1% of the risk distribution has a 4.7-times higher risk of developing PrCa compared with the average of the general population.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts

“…These results also add to existing data as further evidence that genetic features can predict risk of PCa. 6 7 8 11 23 24 25 Investigation into the genotypic features described here and elsewhere could give additional insight into biological rationales for the association with PCa.…”

“…Previous studies have used GWAS-associated polymorphisms to predict risk of PCa with a case-control design. 23 24 25 Epidemiological data, however, show that risk of PCa is not a simple dichotomy of cases and controls but rather is highly dependent on increasing age. We therefore opted for a survival analysis approach optimised for genetic prediction of age of onset of PCa.…”

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

“…However, many expert groups continue to recommend PrCa screening with particular attention towards men with risk factors based on family history, genetics and/or race (Roobol et al, 2013;Eeles et al, 2014;Mikropoulos et al, 2014;Murphy et al, 2014).…”

A genetic risk score to guide age-specific, personalized prostate cancer screening

“…Prior studies have used GWAS-associated polymorphisms to predict risk of PCa using a case/control design [24][25][26] . However, epidemiologic data show that PCa risk is not a simple dichotomy of cases and controls, but rather is highly dependent on increasing age.…”