Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score

Brian T. Helfand, Haitao Chen, Richard J. Fantus, Carly A. Conran, Charles B. Brendler, Siquan Lilly Zheng, Patrick Walsh, William B Isaacs, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1063-1068
Number of pages6
JournalProstate
Volume78
Issue number14
DOIs
StatePublished - Oct 1 2018

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Prostatic Neoplasms
Familial Prostate cancer
Single Nucleotide Polymorphism
Validation Studies
Early Detection of Cancer
Multivariate Analysis
Prospective Studies

Keywords

  • cancer screening
  • family history
  • genetic risk score
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Helfand, B. T., Chen, H., Fantus, R. J., Conran, C. A., Brendler, C. B., Zheng, S. L., ... Xu, J. (2018). Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score. Prostate, 78(14), 1063-1068. https://doi.org/10.1002/pros.23664

Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score. / Helfand, Brian T.; Chen, Haitao; Fantus, Richard J.; Conran, Carly A.; Brendler, Charles B.; Zheng, Siquan Lilly; Walsh, Patrick; Isaacs, William B; Xu, Jianfeng.

In: Prostate, Vol. 78, No. 14, 01.10.2018, p. 1063-1068.

Research output: Contribution to journalArticle

Helfand, BT, Chen, H, Fantus, RJ, Conran, CA, Brendler, CB, Zheng, SL, Walsh, P, Isaacs, WB & Xu, J 2018, 'Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score', Prostate, vol. 78, no. 14, pp. 1063-1068. https://doi.org/10.1002/pros.23664
Helfand BT, Chen H, Fantus RJ, Conran CA, Brendler CB, Zheng SL et al. Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score. Prostate. 2018 Oct 1;78(14):1063-1068. https://doi.org/10.1002/pros.23664
Helfand, Brian T. ; Chen, Haitao ; Fantus, Richard J. ; Conran, Carly A. ; Brendler, Charles B. ; Zheng, Siquan Lilly ; Walsh, Patrick ; Isaacs, William B ; Xu, Jianfeng. / Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score. In: Prostate. 2018 ; Vol. 78, No. 14. pp. 1063-1068.
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AU - Zheng, Siquan Lilly

AU - Walsh, Patrick

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