Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer

Results from the prostate cancer prevention trial

Haitao Chen, Xu Liu, Charles B. Brendler, Donna P. Ankerst, Robin J. Leach, Phyllis J. Goodman, M. Scott Lucia, Catherine M. Tangen, Li Wang, Fang Chi Hsu, Jielin Sun, A. Karim Kader, William B Isaacs, Brian T. Helfand, S. Lilly Zheng, Ian M. Thompson, Elizabeth A Platz, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

BACKGROUND: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. METHODS: A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study. RESULTS: GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10−4 and P = 4.50 × 10−16, respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH− men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 × 10−15). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high-grade PCa cases. CONCLUSIONS: A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120–1129, 2016.

Original languageEnglish (US)
Pages (from-to)1120-1129
Number of pages10
JournalProstate
Volume76
Issue number12
DOIs
StatePublished - Sep 1 2016

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Prostatic Neoplasms
Single Nucleotide Polymorphism
Neoplasm Grading
Genetic Predisposition to Disease
Early Detection of Cancer
Prostate
Decision Making
Placebos

Keywords

  • family history
  • prostate cancer
  • risk
  • single nucleotide polymorphisms
  • the prostate cancer prevention trial

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer : Results from the prostate cancer prevention trial. / Chen, Haitao; Liu, Xu; Brendler, Charles B.; Ankerst, Donna P.; Leach, Robin J.; Goodman, Phyllis J.; Lucia, M. Scott; Tangen, Catherine M.; Wang, Li; Hsu, Fang Chi; Sun, Jielin; Kader, A. Karim; Isaacs, William B; Helfand, Brian T.; Zheng, S. Lilly; Thompson, Ian M.; Platz, Elizabeth A; Xu, Jianfeng.

In: Prostate, Vol. 76, No. 12, 01.09.2016, p. 1120-1129.

Research output: Contribution to journalArticle

Chen, H, Liu, X, Brendler, CB, Ankerst, DP, Leach, RJ, Goodman, PJ, Lucia, MS, Tangen, CM, Wang, L, Hsu, FC, Sun, J, Kader, AK, Isaacs, WB, Helfand, BT, Zheng, SL, Thompson, IM, Platz, EA & Xu, J 2016, 'Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer: Results from the prostate cancer prevention trial', Prostate, vol. 76, no. 12, pp. 1120-1129. https://doi.org/10.1002/pros.23200
Chen, Haitao ; Liu, Xu ; Brendler, Charles B. ; Ankerst, Donna P. ; Leach, Robin J. ; Goodman, Phyllis J. ; Lucia, M. Scott ; Tangen, Catherine M. ; Wang, Li ; Hsu, Fang Chi ; Sun, Jielin ; Kader, A. Karim ; Isaacs, William B ; Helfand, Brian T. ; Zheng, S. Lilly ; Thompson, Ian M. ; Platz, Elizabeth A ; Xu, Jianfeng. / Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer : Results from the prostate cancer prevention trial. In: Prostate. 2016 ; Vol. 76, No. 12. pp. 1120-1129.
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abstract = "BACKGROUND: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. METHODS: A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study. RESULTS: GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10−4 and P = 4.50 × 10−16, respectively). Using FH alone, as expected, the 17{\%} of men who were FH+ had a PCa detection rate that was significantly higher (29.02{\%}) than FH− men (23.43{\%}, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36{\%}) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98{\%}) than in the remaining men (20.61{\%}, P = 5.30 × 10−15). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80{\%}) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45{\%} of high-grade PCa cases. CONCLUSIONS: A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120–1129, 2016.",
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T1 - Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer

T2 - Results from the prostate cancer prevention trial

AU - Chen, Haitao

AU - Liu, Xu

AU - Brendler, Charles B.

AU - Ankerst, Donna P.

AU - Leach, Robin J.

AU - Goodman, Phyllis J.

AU - Lucia, M. Scott

AU - Tangen, Catherine M.

AU - Wang, Li

AU - Hsu, Fang Chi

AU - Sun, Jielin

AU - Kader, A. Karim

AU - Isaacs, William B

AU - Helfand, Brian T.

AU - Zheng, S. Lilly

AU - Thompson, Ian M.

AU - Platz, Elizabeth A

AU - Xu, Jianfeng

PY - 2016/9/1

Y1 - 2016/9/1

N2 - BACKGROUND: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. METHODS: A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study. RESULTS: GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10−4 and P = 4.50 × 10−16, respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH− men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 × 10−15). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high-grade PCa cases. CONCLUSIONS: A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120–1129, 2016.

AB - BACKGROUND: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making. METHODS: A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study. RESULTS: GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10−4 and P = 4.50 × 10−16, respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH− men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 × 10−15). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high-grade PCa cases. CONCLUSIONS: A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120–1129, 2016.

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KW - prostate cancer

KW - risk

KW - single nucleotide polymorphisms

KW - the prostate cancer prevention trial

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