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

被引：31

作者：

Barnes, Daniel R. ^{[1
]}

Silvestri, Valentina ^{[2
]}

Leslie, Goska ^{[1
]}

McGuffog, Lesley ^{[1
]}

Dennis, Joe ^{[1
]}

Yang, Xin ^{[1
]}

Adlard, Julian ^{[3
]}

Agnarsson, Bjarni A. ^{[4
,5
]}

Ahmed, Munaza ^{[6
]}

Aittomaki, Kristiina ^{[7
]}

Andrulis, Irene L. ^{[8
,9
]}

Arason, Adalgeir ^{[4
,10
]}

Arnold, Norbert ^{[11
,12
]}

Auber, Bernd ^{[13
]}

Azzollini, Jacopo ^{[14
]}

Balmana, Judith ^{[15
,16
]}

Barkardottir, Rosa B. ^{[4
,10
]}

Barrowdale, Daniel ^{[1
]}

Barwell, Julian ^{[17
]}

Belotti, Muriel ^{[18
]}

Benitez, Javier ^{[19
,20
]}

Berthet, Pascaline ^{[21
]}

Boonen, Susanne E. ^{[22
]}

Borg, Ake ^{[23
]}

Bozsik, Aniko ^{[24
]}

Brady, Angela F. ^{[25
]}

Brennan, Paul ^{[26
]}

Brewer, Carole ^{[27
]}

Brunet, Joan ^{[28
]}

Bucalo, Agostino ^{[2
]}

Buys, Saundra S. ^{[29
]}

Caldes, Trinidad ^{[30
]}

Caligo, Maria A. ^{[31
]}

Campbell, Ian ^{[32
,33
]}

Cassingham, Hayley ^{[34
]}

Christensen, Lise Lotte ^{[35
]}

Cini, Giulia ^{[36
]}

Claes, Kathleen B. M. ^{[37
]}

Cook, Jackie ^{[41
]}

Coppa, Anna ^{[42
,43
]}

Cortesi, Laura ^{[43
]}

Damante, Giuseppe ^{[44
]}

Darder, Esther ^{[28
]}

Davidson, Rosemarie ^{[45
]}

de la Hoya, Miguel ^{[30
]}

De Leeneer, Kim ^{[37
]}

de Putter, Robin ^{[37
]}

Del Valle, Jesus ^{[28
]}

Diez, Orland ^{[15
,46
]}

Ding, Yuan Chun ^{[47
]}

机构：

[1] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[2] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[3] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England

[4] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland

[5] Univ Iceland, Sch Med, Reykjavik, Iceland

[6] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London, England

[7] Univ Helsinki, Helsinki Univ Hosp, Dept Clin Genet, Helsinki, Finland

[8] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[9] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[10] Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik, Iceland

[11] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany

[12] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Campus Kiel, Kiel, Germany

[13] Hannover Med Sch, Dept Human Genet, Hannover, Germany

[14] Fdn IRCCS Ist Nazl Tumori Milano, Dept Med Oncol & Hematol, Unit Med Genet, Milan, Italy

[15] Vall dHebron Hosp Campus, Hereditary Canc Genet Grp, Vall dHebron Inst Oncol, Barcelona, Spain

[16] Vall dHebron Barcelona Hosp Campus, Dept Med Oncol, Vall dHebron Hosp Univ, Barcelona, Spain

[17] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England

[18] Inst Curie, Serv Genet, Paris, France

[19] Biomed Network Rare Dis CIBERER, Madrid, Spain

[20] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid, Spain

[21] Ctr Francois Baclesse, Epartement Biopathol, Caen, France

[22] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark

[23] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden

[24] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary

[25] London North West Univ Healthcare NHS Trust, North West Thames Reg Genet Serv, Northwick Pk Hosp, Harrow, Middx, England

[26] Newcastle Hosp NHS Fdn Trust, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England

[27] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter, Devon, England

[28] CIBERONC, Catalan Inst Oncol, Oncobell IDIBELL IGTP, Hereditary Canc Program, Barcelona, Spain

[29] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA

[30] Hosp Clin San Carlos, IdISSC Inst Invest Sanitaria Hosp Clin San Carlos, Mol Oncol Lab, CIBERONC, Madrid, Spain

[31] Univ Hosp, Sod Genet Mol, Pisa, Italy

[32] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[33] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[34] Ohio State Univ, Dept Internal Med, Div Human Genet, Wexner Med Ctr, Columbus, OH 43210 USA

[35] Natl Canc Ctr, Div Surg Oncol, Singapore, Singapore

[36] IRCCS, Div Funct Oncogen & Genet, Ctr Riferimento Oncol Aviano CRO, Aviano, Italy

[37] Univ Ghent, Ctr Med Genet, Ghent, Belgium

[38] INSERM U830, Dept Tumour Biol, Paris, France

[39] Inst Curie, Paris, France

[40] Mines ParisTech, Fontainebleau, France

[41] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England

[42] Sapienza Univ Rome, Dept Expt Med, Rome, Italy

[43] Univ Modena & Reggio Emilia, Dept Oncol & Haematol, Modena, Italy

[44] Univ Udine, Dept Med, Udine, Italy

[45] South Glasgow Univ Hosp, Dept Clin Genet, Glasgow, Lanark, Scotland

[46] Vall dHebron Barcelona Hosp Campus, Area Clin & Mol Genet, Vall dHebron Hosp Univ, Barcelona, Spain

[47] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA

[48] Univ Penn, Basser Ctr BRCA, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[49] St Michaels Hosp, Clin Genet Dept, Bristol, Avon, England

[50] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2022年 / 114卷 / 01期

关键词：

MUTATION CARRIERS; ASSOCIATION; OVARIAN;

D O I：

10.1093/jnci/djab147

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：109 / 122

页数：14

共 49 条

[1]

American society of Clinical Oncology, 2017, JAMA-J AM MED ASSOC, DOI DOI 10.1001/JAMA.2017.7112

[2]

[Anonymous], 1967, Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability

[3] RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers:: Results from a combined analysis of 19 studies [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

Simard, Jacques ;

Leone, Melanie ;

Dumont, Martine ;

Neuhausen, Susan L. ;

Struewing, Jeffery P. ;

Stoppa-Lyonnet, Dominique ;

Barjhoux, Laure ;

Hughes, David J. ;

Coupier, Isabelle ;

Belotti, Muriel ;

Lasset, Christine ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Domchek, Susan M. ;

Nathanson, Katherine L. ;

Garber, Judy E. ;

Weitzel, Jeffrey ;

Narod, Steven A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Godwin, Andrew ;

Isaacs, Claudine ;

Jakubowska, Anna ;

Lubinski, Jan ;

Gronwald, Jacek ;

Gorski, Bohdan ;

Byrski, Tomasz ;

Huzarski, Tomasz ;

Peock, Susan ;

Cook, Margaret ;

Baynes, Caroline ;

Murray, Alexandra ;

Rogers, Mark ;

Daly, Peter A. ;

Dorkins, Huw ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Niederacher, Dieter ;

Deissler, Helmut ;

Spurdle, Amanda B. ;

Chen, Xiaoqing ;

Waddell, Nicola ;

Cloonan, Nicole ;

Kirchhoff, Tomas .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (06) :1186-1200

[4] Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction [J].

Antoniou, Antonis C. ;

Beesley, Jonathan ;

McGuffog, Lesley ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Neuhausen, Susan L. ;

Ding, Yuan Chun ;

Rebbeck, Timothy R. ;

Weitzel, Jeffrey N. ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Ganz, Patricia A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Lindor, Noralane M. ;

Pankratz, Vernon S. ;

Radice, Paolo ;

Manoukian, Siranoush ;

Peissel, Bernard ;

Zaffaroni, Daniela ;

Barile, Monica ;

Viel, Alessandra ;

Allavena, Anna ;

Dall'Olio, Valentina ;

Peterlongo, Paolo ;

Szabo, Csilla I. ;

Zikan, Michal ;

Claes, Kathleen ;

Poppe, Bruce ;

Foretova, Lenka ;

Mai, Phuong L. ;

Greene, Mark H. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Glendon, Gord ;

Ozcelik, Hilmi ;

Andrulis, Irene L. ;

Thomassen, Mads ;

Gerdes, Anne-Marie ;

Sunde, Lone ;

Cruger, Dorthe ;

Jensen, Uffe Birk ;

Caligo, Maria ;

Friedman, Eitan ;

Kaufman, Bella ;

Laitman, Yael ;

Milgrom, Roni ;

Dubrovsky, Maya .

CANCER RESEARCH, 2010, 70 (23) :9742-9754

[5] Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants [J].

Barnes, Daniel R. ;

Rookus, Matti A. ;

McGuffog, Lesley ;

Leslie, Goska ;

Mooij, Thea M. ;

Dennis, Joe ;

Mavaddat, Nasim ;

Adlard, Julian ;

Ahmed, Munaza ;

Aittomaki, Kristiina ;

Andrieu, Nadine ;

Andrulis, Irene L. ;

Arnold, Norbert ;

Arun, Banu K. ;

Azzollini, Jacopo ;

Balmana, Judith ;

Barkardottir, Rosa B. ;

Barrowdale, Daniel ;

Benitez, Javier ;

Berthet, Pascaline ;

Bialkowska, Katarzyna ;

Blanco, Amie M. ;

Blok, Marinus J. ;

Bonanni, Bernardo ;

Boonen, Susanne E. ;

Borg, Ake ;

Bozsik, Aniko ;

Bradbury, Angela R. ;

Brennan, Paul ;

Brewer, Carole ;

Brunet, Joan ;

Buys, Saundra S. ;

Caldes, Trinidad ;

Caligo, Maria A. ;

Campbell, Ian ;

Christensen, Lise Lotte ;

Chung, Wendy K. ;

Claes, Kathleen B. M. ;

Colas, Chrystelle ;

Collonge-Rame, Marie-Agnes ;

Cook, Jackie ;

Daly, Mary B. ;

Davidson, Rosemarie ;

de la Hoya, Miguel ;

de Putter, Robin ;

Delnatte, Capucine ;

Devilee, Peter ;

Diez, Orland ;

Ding, Yuan Chun ;

Domchek, Susan M. .

GENETICS IN MEDICINE, 2020, 22 (10) :1653-1666

[6] BRCA1 and BRCA2 mutations in a population-based study of male breast cancer -: art. no. R2 [J].

Basham, VM ;

Lipscombe, JM ;

Ward, JM ;

Gayther, SA ;

Ponder, BAJ ;

Easton, DF ;

Pharoah, PDP .

BREAST CANCER RESEARCH, 2002, 4 (01) :R2

[7] The PROFILE Feasibility Study: Targeted Screening of Men With a Family History of Prostate Cancer [J].

Castro, Elena ;

Mikropoulos, Christos ;

Bancroft, Elizabeth K. ;

Dadaev, Tokhir ;

Goh, Chee ;

Taylor, Natalie ;

Saunders, Edward ;

Borley, Nigel ;

Keating, Diana ;

Page, Elizabeth C. ;

Saya, Sibel ;

Hazell, Stephen ;

Livni, Naomi ;

deSouza, Nandita ;

Neal, David ;

Hamdy, Freddie C. ;

Kumar, Pardeep ;

Antoniou, Antonis C. ;

Kote-Jarai, Zsofia ;

Eeles, Rosalind A. .

ONCOLOGIST, 2016, 21 (06) :716-722

[8] The role of BRCA1 and BRCA2 in prostate cancer [J].

Castro, Elena ;

Eeles, Rosalind .

ASIAN JOURNAL OF ANDROLOGY, 2012, 14 (03) :409-414

[9] An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers:: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2(CIMBA) [J].

Chenevix-Trench, Georgia ;

Milne, Roger L. ;

Antoniou, Antonis C. ;

Couch, Fergus J. ;

Easton, Douglas F. ;

Goldgar, David E. .

BREAST CANCER RESEARCH, 2007, 9 (02)

[10] A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers [J].

Coignard, Juliette ;

Lush, Michael ;

Beesley, Jonathan ;

O'Mara, Tracy A. ;

Dennis, Joe ;

Tyrer, Jonathan P. ;

Barnes, Daniel R. ;

McGuffog, Lesley ;

Leslie, Goska ;

Bolla, Manjeet K. ;

Adank, Muriel A. ;

Agata, Simona ;

Ahearn, Thomas ;

Aittomaeki, Kristiina ;

Andrulis, Irene L. ;

Anton-Culver, Hoda ;

Arndt, Volker ;

Arnold, Norbert ;

Aronson, Kristan J. ;

Arun, Banu K. ;

Augustinsson, Annelie ;

Azzollini, Jacopo ;

Barrowdale, Daniel ;

Baynes, Caroline ;

Becher, Heko ;

Bermisheva, Marina ;

Bernstein, Leslie ;

Bialkowska, Katarzyna ;

Blomqvist, Carl ;

Bojesen, Stig E. ;

Bonanni, Bernardo ;

Borg, Ake ;

Brauch, Hiltrud ;

Brenner, Hermann ;

Burwinkel, Barbara ;

Buys, Saundra S. ;

Caldes, Trinidad ;

Caligo, Maria A. ;

Campa, Daniele ;

Carter, Brian D. ;

Castelao, Jose E. ;

Chang-Claude, Jenny ;

Chanock, Stephen J. ;

Chung, Wendy K. ;

Claes, Kathleen B. M. ;

Clarke, Christine L. ;

Collee, J. Margriet ;

Conroy, Don M. ;

Czene, Kamila ;

Daly, Mary B. .

NATURE COMMUNICATIONS, 2021, 12 (01)

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