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Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score
Author(s) -
Helfand Brian T.,
Chen Haitao,
Fantus Richard J.,
Conran Carly A.,
Brendler Charles B.,
Zheng Siquan Lilly,
Walsh Patrick C.,
Isaacs William B.,
Xu Jianfeng
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23664
Subject(s) - family history , single nucleotide polymorphism , first degree relatives , proband , prostate cancer , medicine , multivariate analysis , oncology , demography , cancer , genetics , genotype , biology , gene , mutation , sociology
Purpose Family 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 Methods Family 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. Results Data 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). Conclusion GRS 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.