Citation
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, et al. (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics, 107(5), 837-848. PMCID: PMC7675034Abstract
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 (PRS(313)) 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 PRS(313) was quantified using Cox regression analyses. We assessed PRS(313) 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 PRS(313) was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS(313) 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 10(th) percentile and 20.5% at the 90(th) percentile of PRS(313). We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS(313) alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS(313) 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.URL
http://dx.doi.org/10.1016/j.ajhg.2020.09.001Reference Type
Journal ArticleYear Published
2020Journal Title
American Journal of Human GeneticsAuthor(s)
Kramer, IrisHooning, 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 Egil
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.
NBCS Collaborators,
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
ABCTB Investigators,
kConFab Investigators,
Ito, Hidemi
Jakimovska, Milena
Jakubowska, Anna
Janni, Wolfgang
John, Esther M.
Jung, Audrey
Kang, Dae-Hee
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
Lubi
ński, 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
L.
Sohn, Christof
Southey, Melissa C
.
Spinelli, John J
.
Stone, Jennifer
Tapper, William J
.
Tengström, Maria
Teo, Soo Hwang
Terry, Mary Beth
Tollenaar, Robert 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
.