Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Barnes, D. R.; Silvestri, V.; Leslie, G.; Mcguffog, L.; Dennis, J.; Yang, X.; Adlard, J.; Agnarsson, B. A.; Ahmed, M.; Aittomaki, K.; Andrulis, I. L.; Arason, A.; Arnold, N.; Auber, B.; Azzollini, J.; Balmana, J.; Barkardottir, R. B.; Barrowdale, D.; Barwell, J.; Belotti, M.; Benitez, J.; Berthet, P.; Boonen, S. E.; Borg, A.; Bozsik, A.; Brady, A. F.; Brennan, P.; Brewer, C.; Brunet, J.; Bucalo, A.; Buys, S. S.; Caldes, T.; Caligo, M. A.; Campbell, I.; Cassingham, H.; Christensen, L. L.; Cini, G.; Claes, K. B. M.; 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.; Ding, Y. C.; Domchek, S. M.; Donaldson, A.; Eason, J.; Eeles, R.; Engel, C.; Evans, D. G.; Feliubadalo, L.; Fostira, F.; Frone, M.; Frost, D.; Gallagher, D.; Gehrig, A.; Giraud, S.; Glendon, G.; Godwin, A. K.; Goldgar, D. E.; Greene, M. H.; Gregory, H.; Gross, E.; Hahnen, E.; Hamann, U.; Hansen, T. V. O.; Hanson, H.; Hentschel, J.; Horvath, J.; Izatt, L.; Izquierdo, A.; James, P. A.; Janavicius, R.; Jensen, U. B.; Johannsson, O. T.; John, E. M.; Kramer, G.; Kroeldrup, L.; Kruse, T. A.; Lautrup, C.; Lazaro, C.; Lesueur, F.; Lopez-Fernandez, A.; Mai, P. L.; Manoukian, S.; Matrai, Z.; Matricardi, L.; Maxwell, K. N.; Mebirouk, N.; Meindl, A.; Montagna, M.; Monteiro, A. N.; Morrison, P. J.; Muranen, T. A.; Murray, A.; Nathanson, K. L.; Neuhausen, S. L.; Nevanlinna, H.; Nguyen-Dumont, T.; Niederacher, D.; Olah, E.; Olopade, O. I.; Palli, D.; Parsons, M. T.; Pedersen, I. S.; Peissel, B.; Perez-Segura, P.; Peterlongo, P.; Petersen, A. H.; Pinto, P.; Porteous, M. E.; Pottinger, C.; Pujana, M. A.; Radice, P.; Ramser, J.; Rantala, J.; Robson, M.; Rogers, M. T.; Ronlund, K.; Rump, A.; Sanchez De Abajo, A. M.; Shah, P. D.; Sharif, S.; Side, L. E.; Singer, C. F.; Stadler, Z.; Steele, L.; Stoppa-Lyonnet, D.; Sutter, C.; Tan, Y. Y.; Teixeira, M. R.; Teule, A.; Thull, D. L.; Tischkowitz, M.; Toland, A. E.; Tommasi, S.; Toss, A.; Trainer, A. H.; Tripathi, V.; Valentini, V.; Van Asperen, C. J.; Venturelli, M.; Viel, A.; Vijai, J.; Walker, L.; Wang-Gohrke, S.; Wappenschmidt, B.; Whaite, A.; Zanna, I.; Offit, K.; Thomassen, M.; Couch, F. J.; Schmutzler, R. K.; Simard, J.; Easton, D. F.; Chenevix-Trench, G.; Antoniou, A. C.; Ottini, L.

doi:10.1093/jnci/djab147

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores / Barnes, D. R.; Silvestri, V.; Leslie, G.; Mcguffog, L.; Dennis, J.; Yang, X.; Adlard, J.; Agnarsson, B. A.; Ahmed, M.; Aittomaki, K.; Andrulis, I. L.; Arason, A.; Arnold, N.; Auber, B.; Azzollini, J.; Balmana, J.; Barkardottir, R. B.; Barrowdale, D.; Barwell, J.; Belotti, M.; Benitez, J.; Berthet, P.; Boonen, S. E.; Borg, A.; Bozsik, A.; Brady, A. F.; Brennan, P.; Brewer, C.; Brunet, J.; Bucalo, A.; Buys, S. S.; Caldes, T.; Caligo, M. A.; Campbell, I.; Cassingham, H.; Christensen, L. L.; Cini, G.; Claes, K. B. M.; 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.; Ding, Y. C.; Domchek, S. M.; Donaldson, A.; Eason, J.; Eeles, R.; Engel, C.; Evans, D. G.; Feliubadalo, L.; Fostira, F.; Frone, M.; Frost, D.; Gallagher, D.; Gehrig, A.; Giraud, S.; Glendon, G.; Godwin, A. K.; Goldgar, D. E.; Greene, M. H.; Gregory, H.; Gross, E.; Hahnen, E.; Hamann, U.; Hansen, T. V. O.; Hanson, H.; Hentschel, J.; Horvath, J.; Izatt, L.; Izquierdo, A.; James, P. A.; Janavicius, R.; Jensen, U. B.; Johannsson, O. T.; John, E. M.; Kramer, G.; Kroeldrup, L.; Kruse, T. A.; Lautrup, C.; Lazaro, C.; Lesueur, F.; Lopez-Fernandez, A.; Mai, P. L.; Manoukian, S.; Matrai, Z.; Matricardi, L.; Maxwell, K. N.; Mebirouk, N.; Meindl, A.; Montagna, M.; Monteiro, A. N.; Morrison, P. J.; Muranen, T. A.; Murray, A.; Nathanson, K. L.; Neuhausen, S. L.; Nevanlinna, H.; Nguyen-Dumont, T.; Niederacher, D.; Olah, E.; Olopade, O. I.; Palli, D.; Parsons, M. T.; Pedersen, I. S.; Peissel, B.; Perez-Segura, P.; Peterlongo, P.; Petersen, A. H.; Pinto, P.; Porteous, M. E.; Pottinger, C.; Pujana, M. A.; Radice, P.; Ramser, J.; Rantala, J.; Robson, M.; Rogers, M. T.; Ronlund, K.; Rump, A.; Sanchez De Abajo, A. M.; Shah, P. D.; Sharif, S.; Side, L. E.; Singer, C. F.; Stadler, Z.; Steele, L.; Stoppa-Lyonnet, D.; Sutter, C.; Tan, Y. Y.; Teixeira, M. R.; Teule, A.; Thull, D. L.; Tischkowitz, M.; Toland, A. E.; Tommasi, S.; Toss, A.; Trainer, A. H.; Tripathi, V.; Valentini, V.; Van Asperen, C. J.; Venturelli, M.; Viel, A.; Vijai, J.; Walker, L.; Wang-Gohrke, S.; Wappenschmidt, B.; Whaite, A.; Zanna, I.; Offit, K.; Thomassen, M.; Couch, F. J.; Schmutzler, R. K.; Simard, J.; Easton, D. F.; Chenevix-Trench, G.; Antoniou, A. C.; Ottini, L.. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 114:1(2022), pp. 109-122. [10.1093/jnci/djab147]

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Barnes D. R.;Silvestri V.;Leslie G.;McGuffog L.;Dennis J.;Yang X.;Adlard J.;Agnarsson B. A.;Ahmed M.;Aittomaki K.;Andrulis I. L.;Arason A.;Arnold N.;Auber B.;Azzollini J.;Balmana J.;Barkardottir R. B.;Barrowdale D.;Barwell J.;Belotti M.;Benitez J.;Berthet P.;Boonen S. E.;Borg A.;Bozsik A.;Brady A. F.;Brennan P.;Brewer C.;Brunet J.;Bucalo A.;Buys S. S.;Caldes T.;Caligo M. A.;Campbell I.;Cassingham H.;Christensen L. L.;Cini G.;Claes K. B. M.;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.;Ding Y. C.;Domchek S. M.;Donaldson A.;Eason J.;Eeles R.;Engel C.;Evans D. G.;Feliubadalo L.;Fostira F.;Frone M.;Frost D.;Gallagher D.;Gehrig A.;Giraud S.;Glendon G.;Godwin A. K.;Goldgar D. E.;Greene M. H.;Gregory H.;Gross E.;Hahnen E.;Hamann U.;Hansen T. V. O.;Hanson H.;Hentschel J.;Horvath J.;Izatt L.;Izquierdo A.;James P. A.;Janavicius R.;Jensen U. B.;Johannsson O. T.;John E. M.;Kramer G.;Kroeldrup L.;Kruse T. A.;Lautrup C.;Lazaro C.;Lesueur F.;Lopez-Fernandez A.;Mai P. L.;Manoukian S.;Matrai Z.;Matricardi L.;Maxwell K. N.;Mebirouk N.;Meindl A.;Montagna M.;Monteiro A. N.;Morrison P. J.;Muranen T. A.;Murray A.;Nathanson K. L.;Neuhausen S. L.;Nevanlinna H.;Nguyen-Dumont T.;Niederacher D.;Olah E.;Olopade O. I.;Palli D.;Parsons M. T.;Pedersen I. S.;Peissel B.;Perez-Segura P.;Peterlongo P.;Petersen A. H.;Pinto P.;Porteous M. E.;Pottinger C.;Pujana M. A.;Radice P.;Ramser J.;Rantala J.;Robson M.;Rogers M. T.;Ronlund K.;Rump A.;Sanchez De Abajo A. M.;Shah P. D.;Sharif S.;Side L. E.;Singer C. F.;Stadler Z.;Steele L.;Stoppa-Lyonnet D.;Sutter C.;Tan Y. Y.;Teixeira M. R.;Teule A.;Thull D. L.;Tischkowitz M.;Toland A. E.;Tommasi S.;Toss A.;Trainer A. H.;Tripathi V.;Valentini V.;Van Asperen C. J.;Venturelli M.;Viel A.;Vijai J.;Walker L.;Wang-Gohrke S.;Wappenschmidt B.;Whaite A.;Zanna I.;Offit K.;Thomassen M.;Couch F. J.;Schmutzler R. K.;Simard J.;Easton D. F.;Chenevix-Trench G.;Antoniou A. C.;Ottini L.

2022

Abstract

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

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Scheda completa

Scheda completa (DC)

	Anno di pubblicazione
	
				2022
			
	Rivista
	
				JOURNAL OF THE NATIONAL CANCER INSTITUTE
			
	N° del Volume
	
				114
			
	Fascicolo
	
				1
			
	Pagina iniziale
	
				109
			
	Pagina finale
	
				122
			
	Codice DOI
	
				https://dx.doi.org/10.1093/jnci/djab147
			
	Codice WoS
	
				WOS:000748167200017
			
	Codice Scopus
	
				2-s2.0-85122613384
			
	Codice PubMed
	
				34320204
			
	Citazione
	
				Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores / Barnes, D. R.; Silvestri, V.; Leslie, G.; Mcguffog, L.; Dennis, J.; Yang, X.; Adlard, J.; Agnarsson, B. A.; Ahmed, M.; Aittomaki, K.; Andrulis, I. L.; Arason, A.; Arnold, N.; Auber, B.; Azzollini, J.; Balmana, J.; Barkardottir, R. B.; Barrowdale, D.; Barwell, J.; Belotti, M.; Benitez, J.; Berthet, P.; Boonen, S. E.; Borg, A.; Bozsik, A.; Brady, A. F.; Brennan, P.; Brewer, C.; Brunet, J.; Bucalo, A.; Buys, S. S.; Caldes, T.; Caligo, M. A.; Campbell, I.; Cassingham, H.; Christensen, L. L.; Cini, G.; Claes, K. B. M.; 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.; Ding, Y. C.; Domchek, S. M.; Donaldson, A.; Eason, J.; Eeles, R.; Engel, C.; Evans, D. G.; Feliubadalo, L.; Fostira, F.; Frone, M.; Frost, D.; Gallagher, D.; Gehrig, A.; Giraud, S.; Glendon, G.; Godwin, A. K.; Goldgar, D. E.; Greene, M. H.; Gregory, H.; Gross, E.; Hahnen, E.; Hamann, U.; Hansen, T. V. O.; Hanson, H.; Hentschel, J.; Horvath, J.; Izatt, L.; Izquierdo, A.; James, P. A.; Janavicius, R.; Jensen, U. B.; Johannsson, O. T.; John, E. M.; Kramer, G.; Kroeldrup, L.; Kruse, T. A.; Lautrup, C.; Lazaro, C.; Lesueur, F.; Lopez-Fernandez, A.; Mai, P. L.; Manoukian, S.; Matrai, Z.; Matricardi, L.; Maxwell, K. N.; Mebirouk, N.; Meindl, A.; Montagna, M.; Monteiro, A. N.; Morrison, P. J.; Muranen, T. A.; Murray, A.; Nathanson, K. L.; Neuhausen, S. L.; Nevanlinna, H.; Nguyen-Dumont, T.; Niederacher, D.; Olah, E.; Olopade, O. I.; Palli, D.; Parsons, M. T.; Pedersen, I. S.; Peissel, B.; Perez-Segura, P.; Peterlongo, P.; Petersen, A. H.; Pinto, P.; Porteous, M. E.; Pottinger, C.; Pujana, M. A.; Radice, P.; Ramser, J.; Rantala, J.; Robson, M.; Rogers, M. T.; Ronlund, K.; Rump, A.; Sanchez De Abajo, A. M.; Shah, P. D.; Sharif, S.; Side, L. E.; Singer, C. F.; Stadler, Z.; Steele, L.; Stoppa-Lyonnet, D.; Sutter, C.; Tan, Y. Y.; Teixeira, M. R.; Teule, A.; Thull, D. L.; Tischkowitz, M.; Toland, A. E.; Tommasi, S.; Toss, A.; Trainer, A. H.; Tripathi, V.; Valentini, V.; Van Asperen, C. J.; Venturelli, M.; Viel, A.; Vijai, J.; Walker, L.; Wang-Gohrke, S.; Wappenschmidt, B.; Whaite, A.; Zanna, I.; Offit, K.; Thomassen, M.; Couch, F. J.; Schmutzler, R. K.; Simard, J.; Easton, D. F.; Chenevix-Trench, G.; Antoniou, A. C.; Ottini, L.. - In: JOURNAL OF THE NATIONAL CANCER INSTITUTE. - ISSN 0027-8874. - 114:1(2022), pp. 109-122. [10.1093/jnci/djab147]
			
	Tutti gli autori
	
						Barnes, D. R.; Silvestri, V.; Leslie, G.; Mcguffog, L.; Dennis, J.; Yang, X.; Adlard, J.; Agnarsson, B. A.; Ahmed, M.; Aittomaki, K.; Andrulis, I. L.;...espandi
						
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