Abstract
Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations.We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods Wegenotyped 1,802male carriers ofBRCA1/2mutations fromthe Consortiumof Investigators ofModifiers of BRCA1/2 by using the custom Illumina OncoArray.We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks formale carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variantswas associatedwith breast cancer risk (odds ratio per standard deviation of PRS, 1.36;95%CI, 1.19 to 1.56; P = 8.6 3 1026). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95%CI, 1.35 to 1.81; P=3.23 1029). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7%to 26%for carriers of BRCA1 mutations and from 19%to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
| Original language | English |
|---|---|
| Pages (from-to) | 2240-2250 |
| Number of pages | 11 |
| Journal | Journal of Clinical Oncology |
| Volume | 35 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - Jul 10 2017 |
ASJC Scopus subject areas
- Oncology
- Cancer Research
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Prediction of breast and prostate cancer risks in male BRCA1 and BRCA2 mutation carriers using polygenic risk scores. / Lecarpentier, Julie; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Leslie, Goska; Lee, Andrew; Al Olama, Ali Amin; Tyrer, Jonathan P.; Frost, Debra; Ellis, Steve; Easton, Douglas F.; Antoniou, Antonis C.; Tischkowitz, Marc; Evans, D. Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai Ren; Walker, Lisa; Side, Lucy E.; Hodgson, Shirley; Izatt, Louise; Eeles, Ros; Orr, Nick; Porteous, Mary E.; Davidson, Rosemarie; Adlard, Julian; Silvestri, Valentina; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Ottini, Laura; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Peterlongo, Paolo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Caligo, Maria A.; Soucy, Penny; Simard, Jacques; Mulligan, Anna Marie; Andrulis, Irene L.; Glendon, Gord; Southey, Melissa; Campbell, Ian; James, Paul; Mitchell, Gillian; Spurdle, Amanda B.; Holland, Helene; Chenevix-Trench, Georgia; John, Esther M.; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L.; Weitzel, Jeffrey N.; Conner, Thomas A.; Buys, Saundra S.; Goldgar, David E.; Godwin, Andrew K.; Sharma, Priyanka; Rebbeck, Timothy R.; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Offit, Kenneth; Loud, Jennifer T.; Greene, Mark H.; Toland, Amanda Ewart; Senter, Leigha; Huo, Dezheng; Nielsen, Sarah M.; Olopade, Olufunmilayo I.; Nathanson, Katherine L.; Domchek, Susan M.; Lorenchick, Christa; Jankowitz, Rachel C.; Couch, Fergus J.; Janavicius, Ramunas; Hansen, Thomas V.O.; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A.; Thomassen, Mads; Osorio, Ana; De La Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Segura, Pedro Perez; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Fostira, Florentia; Hamann, Ute; Sutter, Christian; Meindl, Alfons; Ditsch, Nina; Gehrig, Andrea; Dworniczak, Bernd; Engel, Christoph; Wand, Dorothea; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Wappenschmidt, Barbara; Schmutzler, Rita K.; Kast, Karin; Arnold, Norbert; Wang-Gohrke, Shan; Lasset, Christine; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B.M.; Kiiski, Johanna I.; Khan, Sofia; Nevanlinna, Heli; Aittomaki, Kristiina; Vvan Asperen, Christi J.; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Arason, Adalgeir; Agnarsson, Bjarni A.; Johannsson, Oskar Th; Barkardottir, Rosa B.; Teixeira, Manuel R.; Pinto, Pedro; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung Won; Kang, Eunyoung; Park, Sue Kyung; Kim, Zisun; Tan, Yen Y.; Berger, Andreas; Singer, Christian F.; Yoon, Sook Yee; Teo, Soo Hwang; Von Wachenfeldt, Anna.
In: Journal of Clinical Oncology, Vol. 35, No. 20, 10.07.2017, p. 2240-2250.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Prediction of breast and prostate cancer risks in male BRCA1 and BRCA2 mutation carriers using polygenic risk scores
AU - Lecarpentier, Julie
AU - Kuchenbaecker, Karoline B.
AU - Barrowdale, Daniel
AU - Dennis, Joe
AU - McGuffog, Lesley
AU - Leslie, Goska
AU - Lee, Andrew
AU - Al Olama, Ali Amin
AU - Tyrer, Jonathan P.
AU - Frost, Debra
AU - Ellis, Steve
AU - Easton, Douglas F.
AU - Antoniou, Antonis C.
AU - Tischkowitz, Marc
AU - Evans, D. Gareth
AU - Henderson, Alex
AU - Brewer, Carole
AU - Eccles, Diana
AU - Cook, Jackie
AU - Ong, Kai Ren
AU - Walker, Lisa
AU - Side, Lucy E.
AU - Hodgson, Shirley
AU - Izatt, Louise
AU - Eeles, Ros
AU - Orr, Nick
AU - Porteous, Mary E.
AU - Davidson, Rosemarie
AU - Adlard, Julian
AU - Silvestri, Valentina
AU - Rizzolo, Piera
AU - Navazio, Anna Sara
AU - Valentini, Virginia
AU - Zelli, Veronica
AU - Ottini, Laura
AU - Toss, Angela
AU - Medici, Veronica
AU - Cortesi, Laura
AU - Zanna, Ines
AU - Palli, Domenico
AU - Radice, Paolo
AU - Manoukian, Siranoush
AU - Peissel, Bernard
AU - Azzollini, Jacopo
AU - Peterlongo, Paolo
AU - Viel, Alessandra
AU - Cini, Giulia
AU - Damante, Giuseppe
AU - Tommasi, Stefania
AU - Alducci, Elisa
AU - Tognazzo, Silvia
AU - Montagna, Marco
AU - Caligo, Maria A.
AU - Soucy, Penny
AU - Simard, Jacques
AU - Mulligan, Anna Marie
AU - Andrulis, Irene L.
AU - Glendon, Gord
AU - Southey, Melissa
AU - Campbell, Ian
AU - James, Paul
AU - Mitchell, Gillian
AU - Spurdle, Amanda B.
AU - Holland, Helene
AU - Chenevix-Trench, Georgia
AU - John, Esther M.
AU - Steele, Linda
AU - Ding, Yuan Chun
AU - Neuhausen, Susan L.
AU - Weitzel, Jeffrey N.
AU - Conner, Thomas A.
AU - Buys, Saundra S.
AU - Goldgar, David E.
AU - Godwin, Andrew K.
AU - Sharma, Priyanka
AU - Rebbeck, Timothy R.
AU - Vijai, Joseph
AU - Robson, Mark
AU - Lincoln, Anne
AU - Musinsky, Jacob
AU - Gaddam, Pragna
AU - Offit, Kenneth
AU - Loud, Jennifer T.
AU - Greene, Mark H.
AU - Toland, Amanda Ewart
AU - Senter, Leigha
AU - Huo, Dezheng
AU - Nielsen, Sarah M.
AU - Olopade, Olufunmilayo I.
AU - Nathanson, Katherine L.
AU - Domchek, Susan M.
AU - Lorenchick, Christa
AU - Jankowitz, Rachel C.
AU - Couch, Fergus J.
AU - Janavicius, Ramunas
AU - Hansen, Thomas V.O.
AU - Bojesen, Anders
AU - Nielsen, Henriette Roed
AU - Skytte, Anne Bine
AU - Sunde, Lone
AU - Jensen, Uffe Birk
AU - Pedersen, Inge Sokilde
AU - Krogh, Lotte
AU - Kruse, Torben A.
AU - Thomassen, Mads
AU - Osorio, Ana
AU - De La Hoya, Miguel
AU - Garcia-Barberan, Vanesa
AU - Caldes, Trinidad
AU - Segura, Pedro Perez
AU - Balmaña, Judith
AU - Gutiérrez-Enríquez, Sara
AU - Diez, Orland
AU - Teulé, Alex
AU - Del Valle, Jesús
AU - Feliubadalo, Lidia
AU - Pujana, Miquel Angel
AU - Lazaro, Conxi
AU - Izquierdo, Angel
AU - Darder, Esther
AU - Brunet, Joan
AU - Fostira, Florentia
AU - Hamann, Ute
AU - Sutter, Christian
AU - Meindl, Alfons
AU - Ditsch, Nina
AU - Gehrig, Andrea
AU - Dworniczak, Bernd
AU - Engel, Christoph
AU - Wand, Dorothea
AU - Niederacher, Dieter
AU - Steinemann, Doris
AU - Hahnen, Eric
AU - Hauke, Jan
AU - Rhiem, Kerstin
AU - Wappenschmidt, Barbara
AU - Schmutzler, Rita K.
AU - Kast, Karin
AU - Arnold, Norbert
AU - Wang-Gohrke, Shan
AU - Lasset, Christine
AU - Damiola, Francesca
AU - Barjhoux, Laure
AU - Mazoyer, Sylvie
AU - Stoppa-Lyonnet, Dominique
AU - Belotti, Muriel
AU - Van Heetvelde, Mattias
AU - Poppe, Bruce
AU - De Leeneer, Kim
AU - Claes, Kathleen B.M.
AU - Kiiski, Johanna I.
AU - Khan, Sofia
AU - Nevanlinna, Heli
AU - Aittomaki, Kristiina
AU - Vvan Asperen, Christi J.
AU - Vaszko, Tibor
AU - Kasler, Miklos
AU - Olah, Edith
AU - Arason, Adalgeir
AU - Agnarsson, Bjarni A.
AU - Johannsson, Oskar Th
AU - Barkardottir, Rosa B.
AU - Teixeira, Manuel R.
AU - Pinto, Pedro
AU - Lee, Jong Won
AU - Lee, Min Hyuk
AU - Lee, Jihyoun
AU - Kim, Sung Won
AU - Kang, Eunyoung
AU - Park, Sue Kyung
AU - Kim, Zisun
AU - Tan, Yen Y.
AU - Berger, Andreas
AU - Singer, Christian F.
AU - Yoon, Sook Yee
AU - Teo, Soo Hwang
AU - Von Wachenfeldt, Anna
PY - 2017/7/10
Y1 - 2017/7/10
N2 - Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations.We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods Wegenotyped 1,802male carriers ofBRCA1/2mutations fromthe Consortiumof Investigators ofModifiers of BRCA1/2 by using the custom Illumina OncoArray.We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks formale carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variantswas associatedwith breast cancer risk (odds ratio per standard deviation of PRS, 1.36;95%CI, 1.19 to 1.56; P = 8.6 3 1026). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95%CI, 1.35 to 1.81; P=3.23 1029). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7%to 26%for carriers of BRCA1 mutations and from 19%to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
AB - Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations.We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods Wegenotyped 1,802male carriers ofBRCA1/2mutations fromthe Consortiumof Investigators ofModifiers of BRCA1/2 by using the custom Illumina OncoArray.We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks formale carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variantswas associatedwith breast cancer risk (odds ratio per standard deviation of PRS, 1.36;95%CI, 1.19 to 1.56; P = 8.6 3 1026). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95%CI, 1.35 to 1.81; P=3.23 1029). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7%to 26%for carriers of BRCA1 mutations and from 19%to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
UR - http://www.scopus.com/inward/record.url?scp=85024491245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024491245&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.69.4935
DO - 10.1200/JCO.2016.69.4935
M3 - Article
VL - 35
SP - 2240
EP - 2250
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 20
ER -