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Combined Associations of a Polygenic Risk Score and Classical Risk Factors with Breast Cancer Risk

Citation

Kapoor, Pooja Middha; Mavaddat, Nasim; Choudhury, Parichoy Pal; Wilcox, Amber N.; Lindström, Sara; Behrens, Sabine; Michailidou, Kyriaki; Dennis, Joe G.; Bolla, Manjeet K.; & Wang, Qin, et al. (Online ahead of print). Combined Associations of a Polygenic Risk Score and Classical Risk Factors with Breast Cancer Risk. Journal of the National Cancer Institute. PMCID: PMC Journal - In Process

Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history), and on average 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

URL

http://dx.doi.org/10.1093/jnci/djaa056

Reference Type

Journal Article

Journal Title

Journal of the National Cancer Institute

Author(s)

Kapoor, Pooja Middha
Mavaddat, Nasim
Choudhury, Parichoy Pal
Wilcox, Amber N.
Lindström, Sara
Behrens, Sabine
Michailidou, Kyriaki
Dennis, Joe G.
Bolla, Manjeet K.
Wang, Qin
Jung, Audrey
Abu-Ful, Zomoroda
Ahearn, Thomas
Andrulis, Irene L.
Anton-Culver, Hoda
Arndt, Volker
Aronson, Kristan J.
Auer, Paul L.
Freeman, Laura E. Beane
Becher, Heiko
Beckmann, Matthias W.
Beeghly-Fadiel, Alicia
Benitez, Javier
Bernstein, Leslie
Bojesen, Stig Egil
Brauch, Hiltrud
Brenner, Hermann
Brüning, Thomas
Cai, Qiuyin
Campa, Daniele
Canzian, Federico
Carracedo, Angel
Carter, Brian D.
Castelao, Jose E.
Chanock, Stephen J.
Chatterjee, Nilanjan
Chenevix-Trench, Georgia
Clarke, Christine L.
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Czene, Kamila
Dai, James Y.
Earp, H. Shelton
Ekici, Arif B.
Eliassen, A. Heather
Eriksson, Mikael
Evans, D. Gareth
Fasching, Peter A.
Figueroa, Jonine
Fritschi, Lin
Gabrielson, Marike
Gago-Dominguez, Manuela
Gao, Chi
Gapstur, Susan M.
Gaudet, Mia M.
Giles, Graham G.
González-Neira, Anna
Guénel, Pascal
Haeberle, Lothar
Haiman, Christopher A.
Håkansson, Niclas
Hall, Per
Hamann, Ute
Hatse, Sigrid
Heyworth, Jane
Holleczek, Bernd
Hoover, Robert N.
Hopper, John L.
Howell, Anthony
Hunter, David J.
ABCTB Investigators
kConFab/AOCS Investigators
John, Esther M.
Jones, Michael E.
Kaaks, Rudolf
Keeman, Renske
Kitahara, Cari M.
Ko, Yon-Dschun
Koutros, Stella
Kurian, Allison W.
Lambrechts, Diether
Marchand, Loic Le
Lee, Eunjung
Lejbkowicz, Flavio
Linet, Martha
Lissowska, Jolanta
Llaneza, Ana
MacInnis, Robert J.
Martinez, Maria Elena
Maurer, Tabea
McLean, Catriona
Neuhausen, Susan L.
Newman, William G.
Norman, Aaron
O'Brien, Katie M.
Olshan, Andrew F.
Olson, Janet E.
Olsson, Håkan
Orr, Nick
Perou, Charles M.
Pita, Guillermo
Polley, Eric C.
Prentice, Ross L.
Rennert, Gad
Rennert, Hedy S.
Ruddy, Kathryn J.
Sandler, Dale P.
Saunders, Christobel
Schoemaker, Minouk J.
Schöttker, Ben
Schumacher, Fredrick R.
Scott, Christopher
Scott, Rodney J.
Shu, Xiao-Ou
Smeets, Ann
Southey, Melissa C.
Spinelli, John J.
Stone, Jennifer
Swerdlow, Anthony J.
Tamimi, Rulla M.
Taylor, Jack A.
Troester, Melissa A.
Vachon, Celine M.
van Veen, Elke M.
Wang, Xiaoliang
Weinberg, Clarice R.
Weltens, Caroline
Willett, Walter C.
Winham, Stacey J.
Wolk, Alicja
Yang, Xiaohong R.
Zheng, Wei
Ziogas, Argyrios
Dunning, Alison M.
Pharoah, Paul D. P.
Schmidt, Marjanka K.
Kraft, Peter
Easton, Douglas F.
Milne, Roger L.
García-Closas, Montserrat
Chang-Claude, Jenny

Year Published

Online ahead of print

PMCID

PMC Journal - In Process

Reference ID

12712