It is estimated that in the United States 200,000 men will be diagnosed with prostate cancer each year with approximately 20% to 30% having clinically aggressive prostate cancer. When diagnosed the standard is to consider factors such as Gleason score and tumor stage to assess a man’s prognosis, however there are no biomarkers to identify men at greater risk for developing aggressive prostate cancer. To further our ability to know which men are at higher risks for aggressive prostate cancer some recent research was designed to search for genetic variants associated with the risk of more aggressive disease.
A genome-wide scan was conducted in 202 prostate cancer survivors with a more aggressive phenotype and 100 randomly sampled, age-matched prostate-specific antigen screened negative controls. Analysis of 387,384 autosomal single nucleotide polymorphisms (SNPs) was followed by validation testing in an independent set of 527 cases with more aggressive and 595 cases with less aggressive prostate cancer, and 1,167 age-matched controls.
Results: A variant on 15q13, rs6497287, was confirmed to be most strongly associated with more aggressive (Pdiscovery = 5.20 × 10?5, Pvalidation = 0.004) than less aggressive disease (P = 0.14). Another SNP on 3q26, rs3774315, was found to be associated with prostate cancer risk; however, the association was not stronger for more aggressive disease.
This study provides suggestive evidence for a genetic predisposition to more aggressive prostate cancer and highlights the fact that larger studies are warranted to confirm this supposition and identify further risk variants.
These findings raise the possibility that assessment of genetic variation may one day be useful to discern men at higher risk for developing clinically significant prostate cancer.
Cancer Epidemiol Biomarkers Prev; 20(6); 1196–203. ©2011 AACR.; L.M. FitzGerald, E.M. Kwon, and M.P. Conomos
Joel T Nowak, M.A., M.S.W.