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.; 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.
		
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