Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Iris Kramer; Maartje J Hooning; Nasim Mavaddat; Michael Hauptmann; Renske Keeman; Ewout W Steyerberg; Daniele Giardiello; Antonis C Antoniou; Paul D P Pharoah; Sander Canisius; Zumuruda Abu-Ful; Irene L Andrulis; Hoda Anton-Culver; Kristan J Aronson; Annelie Augustinsson; Heiko Becher; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Natalia V Bogdanova; Stig E Bojesen; Manjeet K Bolla; Bernardo Bonanni; Hiltrud Brauch; Michael Bremer; Sara Y Brucker; Barbara Burwinkel; Jose E Castelao; Tsun L Chan; Jenny Chang-Claude; Stephen J Chanock; Georgia Chenevix-Trench; Ji-Yeob Choi; Christine L Clarke; J Margriet Collée; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Mary B Daly; Peter Devilee; Thilo Dörk; Isabel Dos-Santos-Silva; Alison M Dunning; Miriam Dwek; Diana M Eccles; D Gareth Evans; Peter A Fasching; Henrik Flyger; Manuela Gago-Dominguez; Montserrat García-Closas; José A García-Sáenz; Graham G Giles; David E Goldgar; Anna González-Neira; Christopher A Haiman; Niclas Håkansson; Ute Hamann; Mikael Hartman; Bernadette A M Heemskerk-Gerritsen; Antoinette Hollestelle; John L Hopper; Ming-Feng Hou; Anthony Howell; Hidemi Ito; Milena Jakimovska; Anna Jakubowska; Wolfgang Janni; Esther M John; Audrey Jung; Daehee Kang; C Marleen Kets; Elza Khusnutdinova; Yon-Dschun Ko; Vessela N Kristensen; Allison W Kurian; Ava Kwong; Diether Lambrechts; Loic Le Marchand; Jingmei Li; Annika Lindblom; Jan Lubiński; Arto Mannermaa; Mehdi Manoochehri; Sara Margolin; Keitaro Matsuo; Dimitrios Mavroudis; Alfons Meindl; Roger L Milne; Anna Marie Mulligan; Taru A Muranen; Susan L Neuhausen; Heli Nevanlinna; William G Newman; Andrew F Olshan; Janet E Olson; Håkan Olsson; Tjoung-Won Park-Simon; Julian Peto; Christos Petridis; Dijana Plaseska-Karanfilska; Nadege Presneau; Katri Pylkäs; Paolo Radice; Gad Rennert; Atocha Romero; Rebecca Roylance; Emmanouil Saloustros; Elinor J Sawyer; Rita K Schmutzler; Lukas Schwentner; Christopher Scott; Mee-Hoong See; Mitul Shah; Chen-Yang Shen; Xiao-Ou Shu; Sabine Siesling; Susan Slager; Christof Sohn; Melissa C Southey; John J Spinelli; Jennifer Stone; William J Tapper; Maria Tengström; Soo Hwang Teo; Mary Beth Terry; Rob A E M Tollenaar; Ian Tomlinson; Melissa A Troester; Celine M Vachon; Chantal van Ongeval; Elke M van Veen; Robert Winqvist; Alicja Wolk; Wei Zheng; Argyrios Ziogas; Douglas F Easton; Per Hall; Marjanka K Schmidt; NBCS Collaborators

doi:10.1016/j.ajhg.2020.09.001

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Standard

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. / Kramer, Iris; Hooning, Maartje J; Mavaddat, Nasim; Hauptmann, Michael; Keeman, Renske; Steyerberg, Ewout W; Giardiello, Daniele; Antoniou, Antonis C; Pharoah, Paul D P; Canisius, Sander; Abu-Ful, Zumuruda; Andrulis, Irene L; Anton-Culver, Hoda; Aronson, Kristan J; Augustinsson, Annelie; Becher, Heiko; Beckmann, Matthias W; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Bremer, Michael; Brucker, Sara Y; Burwinkel, Barbara; Castelao, Jose E; Chan, Tsun L; Chang-Claude, Jenny; Chanock, Stephen J; Chenevix-Trench, Georgia; Choi, Ji-Yeob; Clarke, Christine L; Collée, J Margriet; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Evans, D Gareth; Fasching, Peter A; Flyger, Henrik; Gago-Dominguez, Manuela; García-Closas, Montserrat; García-Sáenz, José A; Giles, Graham G; Goldgar, David E; González-Neira, Anna; Haiman, Christopher A; Håkansson, Niclas; Hamann, Ute; Hartman, Mikael; Heemskerk-Gerritsen, Bernadette A M; Hollestelle, Antoinette; Hopper, John L; Hou, Ming-Feng; Howell, Anthony; Ito, Hidemi; Jakimovska, Milena; Jakubowska, Anna; Janni, Wolfgang; John, Esther M; Jung, Audrey; Kang, Daehee; Kets, C Marleen; Khusnutdinova, Elza; Ko, Yon-Dschun; Kristensen, Vessela N; Kurian, Allison W; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lubiński, Jan; Mannermaa, Arto; Manoochehri, Mehdi; Margolin, Sara; Matsuo, Keitaro; Mavroudis, Dimitrios; Meindl, Alfons; Milne, Roger L; Mulligan, Anna Marie; Muranen, Taru A; Neuhausen, Susan L; Nevanlinna, Heli; Newman, William G; Olshan, Andrew F; Olson, Janet E; Olsson, Håkan; Park-Simon, Tjoung-Won; Peto, Julian; Petridis, Christos; Plaseska-Karanfilska, Dijana; Presneau, Nadege; Pylkäs, Katri; Radice, Paolo; Rennert, Gad; Romero, Atocha; Roylance, Rebecca; Saloustros, Emmanouil; Sawyer, Elinor J; Schmutzler, Rita K; Schwentner, Lukas; Scott, Christopher; See, Mee-Hoong; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Siesling, Sabine; Slager, Susan; Sohn, Christof; Southey, Melissa C; Spinelli, John J; Stone, Jennifer; Tapper, William J; Tengström, Maria; Teo, Soo Hwang; Terry, Mary Beth; Tollenaar, Rob A E M; Tomlinson, Ian; Troester, Melissa A; Vachon, Celine M; van Ongeval, Chantal; van Veen, Elke M; Winqvist, Robert; Wolk, Alicja; Zheng, Wei; Ziogas, Argyrios; Easton, Douglas F; Hall, Per; Schmidt, Marjanka K; NBCS Collaborators.

In: AM J HUM GENET, Vol. 107, No. 5, 05.11.2020, p. 837-848.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kramer, I, Hooning, MJ, Mavaddat, N, Hauptmann, M, Keeman, R, Steyerberg, EW, Giardiello, D, Antoniou, AC, Pharoah, PDP, Canisius, S, Abu-Ful, Z, Andrulis, IL, Anton-Culver, H, Aronson, KJ, Augustinsson, A, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Brauch, H, Bremer, M, Brucker, SY, Burwinkel, B, Castelao, JE, Chan, TL, Chang-Claude, J, Chanock, SJ, Chenevix-Trench, G, Choi, J-Y, Clarke, CL, Collée, JM, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Dörk, T, Dos-Santos-Silva, I, Dunning, AM, Dwek, M, Eccles, DM, Evans, DG, Fasching, PA, Flyger, H, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Giles, GG, Goldgar, DE, González-Neira, A, Haiman, CA, Håkansson, N, Hamann, U, Hartman, M, Heemskerk-Gerritsen, BAM, Hollestelle, A, Hopper, JL, Hou, M-F, Howell, A, Ito, H, Jakimovska, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kang, D, Kets, CM, Khusnutdinova, E, Ko, Y-D, Kristensen, VN, Kurian, AW, Kwong, A, Lambrechts, D, Le Marchand, L, Li, J, Lindblom, A, Lubiński, J, Mannermaa, A, Manoochehri, M, Margolin, S, Matsuo, K, Mavroudis, D, Meindl, A, Milne, RL, Mulligan, AM, Muranen, TA, Neuhausen, SL, Nevanlinna, H, Newman, WG, Olshan, AF, Olson, JE, Olsson, H, Park-Simon, T-W, Peto, J, Petridis, C, Plaseska-Karanfilska, D, Presneau, N, Pylkäs, K, Radice, P, Rennert, G, Romero, A, Roylance, R, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schwentner, L, Scott, C, See, M-H, Shah, M, Shen, C-Y, Shu, X-O, Siesling, S, Slager, S, Sohn, C, Southey, MC, Spinelli, JJ, Stone, J, Tapper, WJ, Tengström, M, Teo, SH, Terry, MB, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Vachon, CM, van Ongeval, C, van Veen, EM, Winqvist, R, Wolk, A, Zheng, W, Ziogas, A, Easton, DF, Hall, P, Schmidt, MK & NBCS Collaborators 2020, 'Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk', AM J HUM GENET, vol. 107, no. 5, pp. 837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

APA

Kramer, I., Hooning, M. J., Mavaddat, N., Hauptmann, M., Keeman, R., Steyerberg, E. W., Giardiello, D., Antoniou, A. C., Pharoah, P. D. P., Canisius, S., Abu-Ful, Z., Andrulis, I. L., Anton-Culver, H., Aronson, K. J., Augustinsson, A., Becher, H., Beckmann, M. W., Behrens, S., Benitez, J., ... NBCS Collaborators (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. AM J HUM GENET, 107(5), 837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

Vancouver

Kramer I, Hooning MJ, Mavaddat N, Hauptmann M, Keeman R, Steyerberg EW et al. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. AM J HUM GENET. 2020 Nov 5;107(5):837-848. https://doi.org/10.1016/j.ajhg.2020.09.001

Bibtex

@article{96b41ba077684feeaa6a2420e592c34a,

title = "Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk",

abstract = "Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.",

author = "Iris Kramer and Hooning, {Maartje J} and Nasim Mavaddat and Michael Hauptmann and Renske Keeman and Steyerberg, {Ewout W} and Daniele Giardiello and Antoniou, {Antonis C} and Pharoah, {Paul D P} and Sander Canisius and Zumuruda Abu-Ful and Andrulis, {Irene L} and Hoda Anton-Culver and Aronson, {Kristan J} and Annelie Augustinsson and Heiko Becher and Beckmann, {Matthias W} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Bogdanova, {Natalia V} and Bojesen, {Stig E} and Bolla, {Manjeet K} and Bernardo Bonanni and Hiltrud Brauch and Michael Bremer and Brucker, {Sara Y} and Barbara Burwinkel and Castelao, {Jose E} and Chan, {Tsun L} and Jenny Chang-Claude and Chanock, {Stephen J} and Georgia Chenevix-Trench and Ji-Yeob Choi and Clarke, {Christine L} and Coll{\'e}e, {J Margriet} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Daly, {Mary B} and Peter Devilee and Thilo D{\"o}rk and Isabel Dos-Santos-Silva and Dunning, {Alison M} and Miriam Dwek and Eccles, {Diana M} and Evans, {D Gareth} and Fasching, {Peter A} and Henrik Flyger and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A} and Giles, {Graham G} and Goldgar, {David E} and Anna Gonz{\'a}lez-Neira and Haiman, {Christopher A} and Niclas H{\aa}kansson and Ute Hamann and Mikael Hartman and Heemskerk-Gerritsen, {Bernadette A M} and Antoinette Hollestelle and Hopper, {John L} and Ming-Feng Hou and Anthony Howell and Hidemi Ito and Milena Jakimovska and Anna Jakubowska and Wolfgang Janni and John, {Esther M} and Audrey Jung and Daehee Kang and Kets, {C Marleen} and Elza Khusnutdinova and Yon-Dschun Ko and Kristensen, {Vessela N} and Kurian, {Allison W} and Ava Kwong and Diether Lambrechts and {Le Marchand}, Loic and Jingmei Li and Annika Lindblom and Jan Lubi{\'n}ski and Arto Mannermaa and Mehdi Manoochehri and Sara Margolin and Keitaro Matsuo and Dimitrios Mavroudis and Alfons Meindl and Milne, {Roger L} and Mulligan, {Anna Marie} and Muranen, {Taru A} and Neuhausen, {Susan L} and Heli Nevanlinna and Newman, {William G} and Olshan, {Andrew F} and Olson, {Janet E} and H{\aa}kan Olsson and Tjoung-Won Park-Simon and Julian Peto and Christos Petridis and Dijana Plaseska-Karanfilska and Nadege Presneau and Katri Pylk{\"a}s and Paolo Radice and Gad Rennert and Atocha Romero and Rebecca Roylance and Emmanouil Saloustros and Sawyer, {Elinor J} and Schmutzler, {Rita K} and Lukas Schwentner and Christopher Scott and Mee-Hoong See and Mitul Shah and Chen-Yang Shen and Xiao-Ou Shu and Sabine Siesling and Susan Slager and Christof Sohn and Southey, {Melissa C} and Spinelli, {John J} and Jennifer Stone and Tapper, {William J} and Maria Tengstr{\"o}m and Teo, {Soo Hwang} and Terry, {Mary Beth} and Tollenaar, {Rob A E M} and Ian Tomlinson and Troester, {Melissa A} and Vachon, {Celine M} and {van Ongeval}, Chantal and {van Veen}, {Elke M} and Robert Winqvist and Alicja Wolk and Wei Zheng and Argyrios Ziogas and Easton, {Douglas F} and Per Hall and Schmidt, {Marjanka K} and {NBCS Collaborators}",

year = "2020",

month = nov,

day = "5",

doi = "10.1016/j.ajhg.2020.09.001",

language = "English",

volume = "107",

pages = "837--848",

journal = "AM J HUM GENET",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

RIS

TY - JOUR

T1 - Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

AU - Kramer, Iris

AU - Hooning, Maartje J

AU - Mavaddat, Nasim

AU - Hauptmann, Michael

AU - Keeman, Renske

AU - Steyerberg, Ewout W

AU - Giardiello, Daniele

AU - Antoniou, Antonis C

AU - Pharoah, Paul D P

AU - Canisius, Sander

AU - Abu-Ful, Zumuruda

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Aronson, Kristan J

AU - Augustinsson, Annelie

AU - Becher, Heiko

AU - Beckmann, Matthias W

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bogdanova, Natalia V

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Bonanni, Bernardo

AU - Brauch, Hiltrud

AU - Bremer, Michael

AU - Brucker, Sara Y

AU - Burwinkel, Barbara

AU - Castelao, Jose E

AU - Chan, Tsun L

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J

AU - Chenevix-Trench, Georgia

AU - Choi, Ji-Yeob

AU - Clarke, Christine L

AU - Collée, J Margriet

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Czene, Kamila

AU - Daly, Mary B

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dos-Santos-Silva, Isabel

AU - Dunning, Alison M

AU - Dwek, Miriam

AU - Eccles, Diana M

AU - Evans, D Gareth

AU - Fasching, Peter A

AU - Flyger, Henrik

AU - Gago-Dominguez, Manuela

AU - García-Closas, Montserrat

AU - García-Sáenz, José A

AU - Giles, Graham G

AU - Goldgar, David E

AU - González-Neira, Anna

AU - Haiman, Christopher A

AU - Håkansson, Niclas

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Heemskerk-Gerritsen, Bernadette A M

AU - Hollestelle, Antoinette

AU - Hopper, John L

AU - Hou, Ming-Feng

AU - Howell, Anthony

AU - Ito, Hidemi

AU - Jakimovska, Milena

AU - Jakubowska, Anna

AU - Janni, Wolfgang

AU - John, Esther M

AU - Jung, Audrey

AU - Kang, Daehee

AU - Kets, C Marleen

AU - Khusnutdinova, Elza

AU - Ko, Yon-Dschun

AU - Kristensen, Vessela N

AU - Kurian, Allison W

AU - Kwong, Ava

AU - Lambrechts, Diether

AU - Le Marchand, Loic

AU - Li, Jingmei

AU - Lindblom, Annika

AU - Lubiński, Jan

AU - Mannermaa, Arto

AU - Manoochehri, Mehdi

AU - Margolin, Sara

AU - Matsuo, Keitaro

AU - Mavroudis, Dimitrios

AU - Meindl, Alfons

AU - Milne, Roger L

AU - Mulligan, Anna Marie

AU - Muranen, Taru A

AU - Neuhausen, Susan L

AU - Nevanlinna, Heli

AU - Newman, William G

AU - Olshan, Andrew F

AU - Olson, Janet E

AU - Olsson, Håkan

AU - Park-Simon, Tjoung-Won

AU - Peto, Julian

AU - Petridis, Christos

AU - Plaseska-Karanfilska, Dijana

AU - Presneau, Nadege

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Rennert, Gad

AU - Romero, Atocha

AU - Roylance, Rebecca

AU - Saloustros, Emmanouil

AU - Sawyer, Elinor J

AU - Schmutzler, Rita K

AU - Schwentner, Lukas

AU - Scott, Christopher

AU - See, Mee-Hoong

AU - Shah, Mitul

AU - Shen, Chen-Yang

AU - Shu, Xiao-Ou

AU - Siesling, Sabine

AU - Slager, Susan

AU - Sohn, Christof

AU - Southey, Melissa C

AU - Spinelli, John J

AU - Stone, Jennifer

AU - Tapper, William J

AU - Tengström, Maria

AU - Teo, Soo Hwang

AU - Terry, Mary Beth

AU - Tollenaar, Rob A E M

AU - Tomlinson, Ian

AU - Troester, Melissa A

AU - Vachon, Celine M

AU - van Ongeval, Chantal

AU - van Veen, Elke M

AU - Winqvist, Robert

AU - Wolk, Alicja

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Easton, Douglas F

AU - Hall, Per

AU - Schmidt, Marjanka K

AU - NBCS Collaborators

PY - 2020/11/5

Y1 - 2020/11/5

N2 - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

AB - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

U2 - 10.1016/j.ajhg.2020.09.001

DO - 10.1016/j.ajhg.2020.09.001

M3 - SCORING: Journal article

C2 - 33022221

VL - 107

SP - 837

EP - 848

JO - AM J HUM GENET

JF - AM J HUM GENET

SN - 0002-9297

IS - 5

ER -