Prostate cancer screening using risk stratification based on a multi-state model of genetic variants

Amy Ming Fang Yen, Anssi Auvinen, Johanna Schleutker, Yi Ying Wu, Jean Ching Yuan Fann, Teuvo Tammela, Sam Li Sheng Chen, Sherry Yueh Hsia Chiu, Hsiu His Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Methods Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. Results The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups. Conclusions A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). Prostate 75:825-835, 2015.

Original languageEnglish
Pages (from-to)825-835
Number of pages11
JournalProstate
Volume75
Issue number8
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Genetic Models
Early Detection of Cancer
Prostatic Neoplasms
Prostate-Specific Antigen
Computer Simulation
Population
Genetic Testing
Population Groups
Disease Progression
Prostate
Randomized Controlled Trials
Age Groups

Keywords

  • genetic-variant
  • prostate cancer
  • risk stratification
  • screening

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Yen, A. M. F., Auvinen, A., Schleutker, J., Wu, Y. Y., Fann, J. C. Y., Tammela, T., ... Chen, H. H. (2015). Prostate cancer screening using risk stratification based on a multi-state model of genetic variants. Prostate, 75(8), 825-835. https://doi.org/10.1002/pros.22964

Prostate cancer screening using risk stratification based on a multi-state model of genetic variants. / Yen, Amy Ming Fang; Auvinen, Anssi; Schleutker, Johanna; Wu, Yi Ying; Fann, Jean Ching Yuan; Tammela, Teuvo; Chen, Sam Li Sheng; Chiu, Sherry Yueh Hsia; Chen, Hsiu His.

In: Prostate, Vol. 75, No. 8, 01.06.2015, p. 825-835.

Research output: Contribution to journalArticle

Yen, AMF, Auvinen, A, Schleutker, J, Wu, YY, Fann, JCY, Tammela, T, Chen, SLS, Chiu, SYH & Chen, HH 2015, 'Prostate cancer screening using risk stratification based on a multi-state model of genetic variants', Prostate, vol. 75, no. 8, pp. 825-835. https://doi.org/10.1002/pros.22964
Yen, Amy Ming Fang ; Auvinen, Anssi ; Schleutker, Johanna ; Wu, Yi Ying ; Fann, Jean Ching Yuan ; Tammela, Teuvo ; Chen, Sam Li Sheng ; Chiu, Sherry Yueh Hsia ; Chen, Hsiu His. / Prostate cancer screening using risk stratification based on a multi-state model of genetic variants. In: Prostate. 2015 ; Vol. 75, No. 8. pp. 825-835.
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abstract = "Background Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Methods Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. Results The 10-year risk of having progressive prostate cancer detected ranged from 43{\%} in the top 5{\%} risk group to approximately 11{\%} in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5{\%} risk group and 55 years-old for those in the lower 60{\%} risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups. Conclusions A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). Prostate 75:825-835, 2015.",
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N2 - Background Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Methods Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. Results The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups. Conclusions A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). Prostate 75:825-835, 2015.

AB - Background Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Methods Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. Results The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups. Conclusions A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). Prostate 75:825-835, 2015.

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