Abstract Background Prostate cancer (PCa) is one of the most heritable cancers and a positive family history (FH) of PCa increases risk to 1st degree relatives by over 2 fold. The search for causative genetic variants has led to genome-wide association studies, which have so far identified over 45 susceptibility loci associated with PCa. However, the clinical utility of FH status or PCa risk SNP profiles to predict disease progression or aggression is yet undefined. We explore their potential prognostic role in patients undergoing Active Surveillance (AS). Methods Those enrolled in the Royal Marsden Hospital AS study were eligible. FH was obtained using questionnaires. For those with missing/incomplete data, hospital records were used. Patients with positive FH were further stratified according to the involvement of 1st and/or 2nd degree relatives. For risk score analyses, DNA was genotyped using the Sequenom MassARRAY iPLEX platform and Taqman assays. The cumulative risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies. FH status and the SNP risk scores were analysed separately against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. Results 439 patients were eligible for FH analyses. 31% of those have since undergone treatment and 13% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between FH of PCa in any degree of relation, and biopsy upgrade or time to treatment. For risk score analyses, 391 patients’ DNA were studied. There was also no relationship between the calculated genetic risk scores and biopsy upgrade or time to treatment (p=0.57 and p=0.83 respectively). When analysing differences between the higher and lower genetic risk groups (defined as the top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p=0.85 and p=0.91 respectively). Conclusion FH status or currently known PCa SNP profile risk scores have not been shown to be prognostic factors and should not be used to influence decisions in AS. This is the first study analysing the implications of PCa risk SNPs in AS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4495. doi:1538-7445.AM2012-4495