PGS Publication: PGP000245

Publication Information (EuropePMC)
Title Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.
PubMed ID 34320204(Europe PMC)
doi 10.1093/jnci/djab147
Publication Date July 28, 2021
Journal J Natl Cancer Inst
Author(s) Barnes DR, Silvestri V, Leslie G, McGuffog L, Dennis J, Yang X, Adlard J, Agnarsson BA, Ahmed M, Aittomäki K, Andrulis IL, Arason A, Arnold N, Auber B, Azzollini J, Balmaña J, Barkardottir RB, Barrowdale D, Barwell J, Belotti M, Benitez J, Berthet P, Boonen SE, Borg Å, Bozsik A, Brady A, Brennan P, Brewer C, Brunet J, Bucalo A, Buys SS, Caldés T, Caligo MA, Campbell I, Cassingham H, Lotte Christensen L, Cini G, Claes KBM, GEMO Study Collaborators, EMBRACE Collaborators, Cook J, Coppa A, Cortesi L, Damante G, Darder E, Davidson R, de la Hoya M, De Leeneer K, de Putter R, Del Valle J, Diez O, Chun Ding Y, Domchek SM, Donaldson A, Eason J, Eeles R, Engel C, Gareth Evans D, Feliubadaló L, Fostira F, Frone M, Frost D, Gallagher D, Gehrig A, Giraud S, Glendon G, Godwin AK, Goldgar DE, Greene MH, Gregory H, Gross E, Hahnen E, Hamann U, Hansen TVO, Hanson H, Hentschel J, Horvath J, KConFab Investigators, HEBON Investigators, Izatt L, Izquierdo A, James PA, Janavicius R, Birk Jensen U, Johannsson OT, John EM, Kramer G, Kroeldrup L, Kruse TA, Lautrup C, Lazaro C, Lesueur F, Lopez-Fernández A, Mai PL, Manoukian S, Matrai Z, Matricardi L, Maxwell KN, Mebirouk N, Meindl A, Montagna M, Monteiro AN, Morrison PJ, Muranen TA, Murray A, Nathanson KL, Neuhausen SL, Nevanlinna H, Nguyen-Dumont T, Niederacher D, Olah E, Olopade OI, Palli D, Parsons MT, Sokilde Pedersen I, Peissel B, Perez-Segura P, Peterlongo P, Petersen AH, Pinto P, Porteous ME, Pottinger C, Angel Pujana M, Radice P, Ramser J, Rantala J, Robson M, Rogers MT, Rønlund K, Rump A, María Sánchez de Abajo A, Shah PD, Sharif S, Side LE, Singer CF, Stadler Z, Steele L, Stoppa-Lyonnet D, Sutter C, Yen Tan Y, Teixeira MR, Teulé A, Thull DL, Tischkowitz M, Toland AE, Tommasi S, Toss A, Trainer AH, Tripathi V, Valentini V, van Asperen CJ, Venturelli M, Viel A, Vijai J, Walker L, Wang-Gohrke S, Wappenschmidt B, Whaite A, Zanna I, Offit K, Thomassen M, Couch FJ, Schmutzler RK, Simard J, Easton DF, Chenevix-Trench G, Antoniou AC, Ottini L, Consortium of Investigators of Modifiers of BRCA1 and BRCA2.
Released in PGS Catalog: Nov. 4, 2021

Associated Polygenic Score(s)

Filter PGS by Participant Ancestry
Individuals included in:
G - Source of Variant Associations (GWAS)
D - Score Development/Training
E - PGS Evaluation
List of ancestries includes:
Display options:
Ancestry legend
Multi-ancestry (including European)
Multi-ancestry (excluding European)
African
East Asian
South Asian
Additional Asian Ancestries
European
Greater Middle Eastern
Hispanic or Latin American
Additional Diverse Ancestries
Not Reported

External PGS Evaluated By This Publication

Polygenic Score ID & Name PGS Publication ID (PGP) Reported Trait Mapped Trait(s) (Ontology) Number of Variants Ancestry distribution
GWAS
Dev
Eval
 Scoring File (FTP Link)
PGS000004
(PRS313_BC)
 PGP000002 |
Mavaddat N et al. Am J Hum Genet (2018)
 Breast cancer breast carcinoma 313
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000004/ScoringFiles/PGS000004.txt.gz
PGS000005
(PRS313_ERpos)
 PGP000002 |
Mavaddat N et al. Am J Hum Genet (2018)
 ER-positive breast cancer estrogen-receptor positive breast cancer 313
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000005/ScoringFiles/PGS000005.txt.gz
PGS000030
(PrCa)
 PGP000019 |
Schumacher FR et al. Nat Genet (2018)
 Prostate cancer prostate carcinoma 147
-
 https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000030/ScoringFiles/PGS000030.txt.gz
PGS000006
(PRS313_ERneg)
 PGP000002 |
Mavaddat N et al. Am J Hum Genet (2018)
 ER-negative breast cancer estrogen-receptor negative breast cancer 313
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000006/ScoringFiles/PGS000006.txt.gz

Performance Metrics

Disclaimer: The performance metrics are displayed as reported by the source studies. It is important to note that metrics are not necessarily comparable with each other. For example, metrics depend on the sample characteristics (described by the PGS Catalog Sample Set [PSS] ID), phenotyping, and statistical modelling. Please refer to the source publication for additional guidance on performance.

PGS Performance
Metric ID (PPM) 		Evaluated Score PGS Sample Set ID
(PSS) 		Performance Source Trait PGS Effect Sizes
(per SD change) 		Classification Metrics Other Metrics Covariates Included in the Model PGS Performance:
Other Relevant Information
PPM005118 PGS000004
(PRS313_BC)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA1 carriers OR: 1.4 [1.06, 1.85] — — PCs(1-3) —
PPM005127 PGS000005
(PRS313_ERpos)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA1 carriers OR: 1.4 [1.07, 1.83] AUROC: 0.6 [0.51, 0.69] — PCs(1-3) —
PPM005128 PGS000005
(PRS313_ERpos)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA1 carriers OR: 1.39 [1.06, 1.82] — — PCs(1-3), family history of male breast cancer in first and second degree relatives —
PPM005129 PGS000005
(PRS313_ERpos)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA1 carriers OR: 1.46 [1.09, 1.94] — — PCs(1-3), family history of female breast cancer in first and second degree relatives —
PPM005130 PGS000005
(PRS313_ERpos)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA2 carriers OR: 1.33 [1.16, 1.52] AUROC: 0.59 [0.55, 0.63] — PCs(1-3) —
PPM005131 PGS000005
(PRS313_ERpos)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA2 carriers OR: 1.33 [1.16, 1.53] — — PCs(1-3), family history of male breast cancer in first and second degree relatives —
PPM005133 PGS000030
(PrCa)
 PSS003583|
European Ancestry|
450 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Prostate cancer in BRCA1 carriers OR: 1.73 [1.28, 2.33] AUROC: 0.62 [0.54, 0.69] — PCs(1-3) —
PPM005134 PGS000030
(PrCa)
 PSS003583|
European Ancestry|
450 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Prostate cancer in BRCA1 carriers OR: 1.74 [1.29, 2.35] — — PCs(1-3), family history of prostate cancer in first and second degree relatives —
PPM005135 PGS000030
(PrCa)
 PSS003584|
European Ancestry|
1,074 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Prostate cancer in BRCA2 carriers OR: 1.6 [1.34, 1.91] AUROC: 0.62 [0.57, 0.67] — PCs(1-3) —
PPM005136 PGS000030
(PrCa)
 PSS003584|
European Ancestry|
1,074 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Prostate cancer in BRCA2 carriers OR: 1.59 [1.32, 1.9] — — PCs(1-3), family history of prostate cancer in first and second degree relatives —
PPM005124 PGS000006
(PRS313_ERneg)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor negative breast cancer in BRCA2 carriers OR: 1.23 [1.07, 1.41] — — PCs(1-3) —
PPM005125 PGS000006
(PRS313_ERneg)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor negative breast cancer in BRCA2 carriers OR: 1.23 [1.07, 1.42] — — PCs(1-3), family history of male breast cancer in first and second degree relatives —
PPM005119 PGS000004
(PRS313_BC)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA1 carriers OR: 1.39 [1.05, 1.84] — — PCs(1-3), family history of male breast cancer in first and second degree relatives —
PPM005120 PGS000004
(PRS313_BC)
 PSS003581|
European Ancestry|
413 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA1 carriers OR: 1.44 [1.07, 1.95] — — PCs(1-3), family history of female breast cancer in first and second degree relatives —
PPM005121 PGS000004
(PRS313_BC)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA2 carriers OR: 1.32 [1.15, 1.52] — — PCs(1-3) —
PPM005122 PGS000004
(PRS313_BC)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA2 carriers OR: 1.33 [1.15, 1.52] — — PCs(1-3), family history of male breast cancer in first and second degree relatives —
PPM005123 PGS000004
(PRS313_BC)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male breast cancer in BRCA2 carriers OR: 1.36 [1.18, 1.57] — — PCs(1-3), family history of female breast cancer in first and second degree relatives —
PPM005126 PGS000006
(PRS313_ERneg)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor negative breast cancer in BRCA2 carriers OR: 1.25 [1.09, 1.45] — — PCs(1-3), family history of female breast cancer in first and second degree relatives —
PPM005132 PGS000005
(PRS313_ERpos)
 PSS003582|
European Ancestry|
1,177 individuals
 PGP000245 |
Barnes DR et al. J Natl Cancer Inst (2021)
|Ext.		 Reported Trait: Male estrogen receptor positive breast cancer in BRCA2 carriers OR: 1.36 [1.18, 1.57] — — PCs(1-3), family history of female breast cancer in first and second degree relatives —

Evaluated Samples

PGS Sample Set ID
(PSS) 		Phenotype Definitions and Methods Participant Follow-up Time Sample Numbers Age of Study Participants Sample Ancestry Additional Ancestry Description Cohort(s) Additional Sample/Cohort Information
PSS003584 All individuals were BRCA2 carriers. BRCA2 pathogenic variants were categorized according to their known or predicted effect on protein function: “class I” included loss-of-function variants expected to yield unstable or no protein; “class II” included variants likely to produce stable mutant proteins. Pathology data were obtained from pathology reviews, medical, pathology or tumor registry records, or immunohistochemical staining of tissue microarrays. All cases were individuals with prostate cancer. —
[
  • 141 cases
  • , 933 controls
]
,
100.0 % Male samples
 — European — 36 cohorts
  • BCFR
  • ,BCFR-AU
  • ,BCFR-CA
  • ,BCFR-UT
  • ,BRICOH
  • ,CBCS
  • ,CNIO
  • ,CONSIT_TEAM
  • ,DKFZ
  • ,EMBRACE
  • ,FCCC
  • ,G-FaST
  • ,GC-HBOC
  • ,GEMO
  • ,HCSC
  • ,HEBCS
  • ,HEBON
  • ,HUNBOCS
  • ,HVH
  • ,ICO
  • ,ILUH
  • ,IOVHBOCS
  • ,IPOBCS
  • ,MAYO
  • ,MSKCC
  • ,MUV
  • ,NCI
  • ,OCGN
  • ,OSUCCG
  • ,OUH
  • ,PBCS
  • ,SWE-BRCA
  • ,UPENN
  • ,UPITT
  • ,VFCTG
  • ,kConFab
 Additional cases and controls were obtained from UCHICAGO
PSS003581 All individuals were BRCA1 carriers. BRCA1 pathogenic variants were categorized according to their known or predicted effect on protein function: “class I” included loss-of-function variants expected to yield unstable or no protein; “class II” included variants likely to produce stable mutant proteins. Pathology data were obtained from pathology reviews, medical, pathology or tumor registry records, or immunohistochemical staining of tissue microarrays. All cases were individuals with breast cancer. —
[
  • 33 cases
  • , 380 controls
]
,
100.0 % Male samples
 — European — 28 cohorts
  • BCFR
  • ,BCFR-CA
  • ,BCFR-UT
  • ,BFBOCC
  • ,BRICOH
  • ,CBCS
  • ,CNIO
  • ,CONSIT_TEAM
  • ,DEMOKRITOS
  • ,DKFZ
  • ,EMBRACE
  • ,FCCC
  • ,GC-HBOC
  • ,GEMO
  • ,HEBCS
  • ,HEBON
  • ,HUNBOCS
  • ,HVH
  • ,ICO
  • ,MAYO
  • ,MSKCC
  • ,MUV
  • ,OCGN
  • ,OSUCCG
  • ,SWE-BRCA
  • ,UPENN
  • ,VFCTG
  • ,kConFab
 Additional controls were obtained from UCHICAGO
PSS003582 All individuals were BRCA2 carriers. BRCA2 pathogenic variants were categorized according to their known or predicted effect on protein function: “class I” included loss-of-function variants expected to yield unstable or no protein; “class II” included variants likely to produce stable mutant proteins. Pathology data were obtained from pathology reviews, medical, pathology or tumor registry records, or immunohistochemical staining of tissue microarrays. All cases were individuals with breast cancer. —
[
  • 244 cases
  • , 933 controls
]
,
100.0 % Male samples
 — European — 35 cohorts
  • BCFR
  • ,BCFR-CA
  • ,BCFR-UT
  • ,BRICOH
  • ,CNIO
  • ,CONSIT_TEAM
  • ,DEMOKRITOS
  • ,DKFZ
  • ,EMBRACE
  • ,FCCC
  • ,G-FaST
  • ,GC-HBOC
  • ,GEMO
  • ,HCSC
  • ,HEBCS
  • ,HEBON
  • ,HUNBOCS
  • ,HVH
  • ,ICO
  • ,ILUH
  • ,IOVHBOCS
  • ,IPOBCS
  • ,MAYO
  • ,MSKCC
  • ,MUV
  • ,NCI
  • ,OCGN
  • ,OSUCCG
  • ,OUH
  • ,PBCS
  • ,SWE-BRCA
  • ,UPENN
  • ,UPITT
  • ,VFCTG
  • ,kConFab
 Additional controls were obtained from UCHICAGO
PSS003583 All individuals were BRCA1 carriers. BRCA1 pathogenic variants were categorized according to their known or predicted effect on protein function: “class I” included loss-of-function variants expected to yield unstable or no protein; “class II” included variants likely to produce stable mutant proteins. Pathology data were obtained from pathology reviews, medical, pathology or tumor registry records, or immunohistochemical staining of tissue microarrays. All cases were individuals with prostate cancer. —
[
  • 70 cases
  • , 380 controls
]
,
100.0 % Male samples
 — European — 31 cohorts
  • BCFR
  • ,BCFR-CA
  • ,BCFR-UT
  • ,BFBOCC
  • ,BRICOH
  • ,CBCS
  • ,CNIO
  • ,CONSIT_TEAM
  • ,DEMOKRITOS
  • ,DKFZ
  • ,EMBRACE
  • ,FCCC
  • ,GC-HBOC
  • ,GEMO
  • ,HEBCS
  • ,HUNBOCS
  • ,HVH
  • ,ICO
  • ,IOVHBOCS
  • ,MAYO
  • ,MSKCC
  • ,MUV
  • ,NCI
  • ,OCGN
  • ,OSUCCG
  • ,OUH
  • ,SWE-BRCA
  • ,UPENN
  • ,UPITT
  • ,VFCTG
  • ,kConFab
 Additional cases and controls were obtained from UCHICAGO