A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

被引：28

作者：

Huynh-Le, Minh-Phuong ^{[1
,2
]}

Fan, Chun Chieh ^{[2
]}

Karunamuni, Roshan ^{[1
,2
]}

Walsh, Eleanor, I ^{[3
]}

Turner, Emma L. ^{[3
]}

Lane, J. Athene ^{[3
,4
]}

Martin, Richard M. ^{[3
,4
,5
,6
]}

Neal, David E. ^{[7
,8
,9
]}

Donovan, Jenny L. ^{[10
]}

Hamdy, Freddie C. ^{[7
,11
]}

Parsons, J. Kellogg ^{[12
]}

Eeles, Rosalind A. ^{[13
,14
]}

Easton, Douglas F. ^{[15
]}

Kote-Jarai, Zsofia ^{[13
]}

Al Olama, Ali Amin ^{[15
,16
]}

Garcia, Sara Benlloch ^{[15
]}

Muir, Kenneth ^{[17
,18
]}

Gronberg, Henrik ^{[19
]}

Wiklund, Fredrik ^{[19
]}

Aly, Markus ^{[19
,20
,21
]}

Schleutker, Johanna ^{[22
,23
]}

Sipeky, Csilla ^{[22
]}

Tammela, Teuvo L. J. ^{[24
,25
]}

Nordestgaard, Borge Gronne ^{[26
,27
]}

Key, Timothy J. ^{[28
]}

Travis, Ruth C. ^{[28
]}

Pharoah, Paul Dp ^{[29
]}

Pashayan, Nora ^{[29
,30
]}

Khaw, Kay-Tee ^{[31
]}

Thibodeau, Stephen N. ^{[32
]}

McDonnell, Shannon K. ^{[33
]}

Schaid, Daniel J. ^{[33
]}

Maier, Christiane ^{[34
]}

Vogel, Walther ^{[35
]}

Luedeke, Manuel ^{[34
]}

Herkommer, Kathleen ^{[36
]}

Kibel, Adam S. ^{[37
]}

Cybulski, Cezary ^{[38
]}

Wokolorczyk, Dominika ^{[38
]}

Kluzniak, Wojciech ^{[38
]}

Cannon-Albright, Lisa A. ^{[39
,40
]}

Brenner, Hermann ^{[41
,42
,43
,44
]}

Ben Schoettker ^{[41
,45
]}

Holleczek, Bernd ^{[41
,46
]}

Park, Jong Y. ^{[47
]}

Sellers, Thomas A. ^{[47
]}

Lin, Hui-Yi ^{[48
]}

Slavov, Chavdar Kroumov ^{[49
,50
]}

Kaneva, Radka P. ^{[51
]}

Mitev, Vanio, I ^{[51
]}

机构：

[1] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Ctr Multimodal Imaging & Genet, La Jolla, CA 92093 USA

[3] Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol, Avon, England

[4] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[5] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res NIHR, Bristol Biomed Res Ctr, Bristol, Avon, England

[6] Univ Bristol, Bristol, Avon, England

[7] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England

[8] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge, England

[9] Cambridge Res Inst, Li Ka Shing Ctr, Canc Res UK, Cambridge, England

[10] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[11] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford, England

[12] Univ Calif San Diego, Dept Urol, La Jolla, CA 92093 USA

[13] Inst Canc Res, London, England

[14] Royal Marsden NHS Fdn Trust, London, England

[15] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Cambridge, England

[16] Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge, England

[17] Univ Manchester, Div Populat Hlth Hlth Serv Res & Primary Care, Oxford Rd, Manchester, Lancs, England

[18] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

[19] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[20] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[21] Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden

[22] Univ Turku, Inst Biomed, Turku, Finland

[23] Turku Univ Hosp, Dept Med Genet, Lab Div, Genom, Turku, Finland

[24] Tampere Univ, Fac Med & Hlth Technol, Prostate Canc Res Ctr, Tampere, Finland

[25] Univ Tampere, Dept Urol, Tampere, Finland

[26] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[27] Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Copenhagen, Denmark

[28] Univ Oxford, Oxford, England

[29] Univ Cambridge, Ctr Canc Genet Epidemiol, Strangeways Lab, Dept Oncol, Cambridge, England

[30] UCL, Dept Appl Hlth Res, London, England

[31] Univ Cambridge, Clin Gerontol Unit, Cambridge, England

[32] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[33] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA

[34] Humangenet Tuebingen, Tubingen, Germany

[35] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany

[36] Tech Univ Munich, Sch Med, Dept Urol, Klinikum Rechts Isar, Munich, Germany

[37] Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA

[38] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland

[39] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA

[40] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA

[41] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[42] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[43] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[44] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[45] Heidelberg Univ, Network Aging Res, Heidelberg, Germany

[46] Saarland Canc Registry, Saarbrucken, Germany

[47] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

[48] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA USA

[49] Med Univ Sofia, Dept Urol, Sofia, Bulgaria

[50] Med Univ Sofia, Alexandrovska Univ Hosp, Sofia, Bulgaria

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2020年 / 29卷 / 09期

关键词：

MORTALITY; AGE;

D O I：

10.1158/1055-9965.EPI-19-1527

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score >= 7, stage T3-T4, PSA >= 10, or nodal/distant meta-stases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

引用

页码：1731 / 1738

页数：8

共 41 条

[41] American Cancer Society Guideline for the Early Detection of Prostate Cancer Update 2010 [J].

Wolf, Andrew M. D. ;

Wender, Richard C. ;

Etzioni, Ruth B. ;

Thompson, Ian M. ;

D'Amico, Anthony V. ;

Volk, Robert J. ;

Brooks, Durado D. ;

Dash, Chiranjeev ;

Guessous, Idris ;

Andrews, Kimberly ;

DeSantis, Carol ;

Smith, Robert A. .

CA-A CANCER JOURNAL FOR CLINICIANS, 2010, 60 (02) :70-98

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