PurposeFamily history assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine prostate cancer (PCa) risk. We sought to determine whether GRS can stratify PCa risk among individuals in families considered to be at higher risk due their family history of PCa. Materials and MethodsFamily members with hereditary PCa were recruited and genotyped for 17 SNPs associated with PCa. A GRS was calculated for all subjects. Analyses compared the distribution of GRS values among affected and unaffected family members of varying relationship degrees. ResultsData was available for 789 family members of probands including 552 affected and 237 unaffected relatives. Median GRSs were higher among first-degree relatives compared to second- and third-degree relatives. In addition, GRS values among affected first- and second-degree relatives were significantly higher than unaffected relatives (P=0.042 and P=0.016, respectively). Multivariate analysis including GRS and degree of relationship demonstrated that GRS was a significant and independent predictor of PCa (OR 1.52, 95%CI 1.15-2.01). ConclusionGRS is an easy-to-interpret, objective measure that can be used to assess differences in PCa risk among family members of affected men. GRS allows for further differentiation among family members, providing better risk assessment. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening.
[1]NorthShore Univ HealthSyst, Div Urol, John & Carol Walter Urol Hlth, Evanston, IL 60201 USA;
[2]Fudan Univ, Sch Publ Hlth, Ctr Genom Translat Med & Prevent, Shanghai, Peoples R China;
[3]Univ Chicago, Med Ctr, Dept Surg, Urol Sect, Chicago, IL 60637 USA;
[4]Johns Hopkins Univ, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21218 USA
(8.0+极速模式)