Login to Access Video or Poster Abstract: MP33-11
Sources of Funding: none

Introduction

Family history is a well-established risk factor for prostate cancer (PCa). However, family history information 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 an individual&[prime]s PCa risk. We sought to determine whether GRS can better estimate PCa risk among individuals with a family history of PCa.

Methods

Patients evaluated at a tertiary referral clinic with a family history of PCa were recruited for this study and were genotyped for 26 SNPs previously associated with PCa. The degree of familial risk (F) was calculated for each subject based on PCa among his relatives (e.g. F value of 0.5= 1 first-degree relative with PCa or 2 second-degree relatives with PCa). A GRS value was also calculated for each subject using 26 SNPs. Analyses comparing the distribution of GRS values among affected and unaffected family members with varying F values were performed.

Results

Subjects from 811 families with at least two affected members were included. The median GRS was significantly higher among family members with PCa (median 1.31; range 0.21-11.64) compared to unaffected family members (median 1.03; range 0.18-6.32; p=9.69e-8). There was a wide distribution of GRS values among members of each F group (Table). Higher GRS values were significantly associated with increased PCa risk among all F groups (p<0.05). For example, among subjects with F values of 1-1.49, PCa patients had a high mean GRS (1.64) than non-PCa subjects (1.12), P=0.0015. Multivariate models to assess the associations between age, GRS, F value and PCa diagnosis demonstrate that higher GRS (P=1.36e-7) and higher F values (P=2.64e-9) were independently associated with increased PCa risk.

Conclusions

GRS is an objective measurement that allows for differentiation of PCa risk among family members with similar degrees of familial risk of PCa. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening.

Funding

none