Number of prostate cancer risk alleles may identify possibly 'insignificant' disease.

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To determine whether the cumulative effects of five prostate cancer risk alleles (three single-nucleotide polymorphisms [SNPs] on chromosome 8Q24 and two SNPs on chromosome 17a) could help to identify possibly ‘insignificant’ disease. MATERIALS AND METHODS We genotyped 629 men of European ancestry who underwent radical prostatectomy at our institution between 2002 and 2007. Possibly ‘insignificant’ CaP was defined using the Ohori criteria (organ-confined, tumour volume <0.5 mL, Gleason pattern ≤4). Statistical analysis was used to compare patients with ‘insignificant’ and all other ‘significant’ cancer based upon genotype. Carrier status for the 5 SNPs were compared between patients with ‘insignificant’ disease and a separate population of 801 controls without CaP. RESULTS Overall, 38 (6.0%) patients with CaP met the Ohori criteria for ‘insignificant’ disease. Men with ‘significant’ cancer had a greater frequency of any of the five risk alleles than either patients with ‘insignificant’ disease or controls. None of the individual alleles genotyped on chromosomes 8 or 17 distinguished between ‘significant’ and ‘insignificant’ CaP. However, carriers of two or more risk alleles were more likely to have ‘significant’ disease. CONCLUSIONS Although no single risk allele distinguished ‘insignificant’ CaP, ‘insignificant’ disease was nearly three times as likely among carriers of ≤ one risk allele. Future studies are needed to further elucidate the cumulative relationship between CaP risk alleles and CaP aggressiveness.