Germline variation at 8q24 and prostate cancer risk in men of European ancestry.

Change log
Matejcic, Marco 
Saunders, Edward J 

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine 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 identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three 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 have a 4-fold (95%CI = 3.62-4.40) 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.

Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 8, Disease Susceptibility, Genetic Markers, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Prostatic Neoplasms, Risk Assessment, Risk Factors, White People
Journal Title
Nat Commun
Conference Name
Journal ISSN
Volume Title
Springer Science and Business Media LLC
Cancer Research Uk (None)
National Cancer Institute (U19CA148537)
Medical Research Council (G0401527)
Medical Research Council (G1000143)
Medical Research Council (MR/N003284/1)
Cancer Research Uk (None)
European Commission (223175)
Cancer Research UK (A16563)
Cancer Research UK (A10118)