Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. In this study, we combined genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identified 12 independent risk signals for prostate cancer (P<4.28x10-15), including three novel risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS had a 4-fold (95%CI=3.87-4.07) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.
1 Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
2 The Institute of Cancer Research, London, UK
83 Royal Marsden NHS Foundation Trust, London, UK
+ These are co-first authors
++ These are joint senior authors
x Corresponding author
Using runGitHub() within RStudio
Open RStudio (start a new R session) copy the following code into the console and hit Return:
library(shiny)
runGitHub("8q24", "oncogenetics", launch.browser = TRUE)