TY - JOUR
T1 - Combined Associations of a Polygenic Risk Score and Classical Risk Factors with Breast Cancer Risk
AU - ABCTB Investigators
AU - kConFab/AOCS Investigators
AU - Kapoor, Pooja Middha
AU - Mavaddat, Nasim
AU - Choudhury, Parichoy Pal
AU - Wilcox, Amber N.
AU - Lindström, Sara
AU - Behrens, Sabine
AU - Michailidou, Kyriaki
AU - Dennis, Joe
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Jung, Audrey
AU - Abu-Ful, Zomoroda
AU - Ahearn, Thomas
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Aronson, Kristan J.
AU - Auer, Paul L.
AU - Freeman, Laura E.Beane
AU - Becher, Heiko
AU - Beckmann, Matthias W.
AU - Beeghly-Fadiel, Alicia
AU - Benitez, Javier
AU - Bernstein, Leslie
AU - Bojesen, Stig E.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brüning, Thomas
AU - Cai, Qiuyin
AU - Campa, Daniele
AU - Canzian, Federico
AU - Carracedo, Angel
AU - Carter, Brian D.
AU - Castelao, Jose E.
AU - Chanock, Stephen J.
AU - Chatterjee, Nilanjan
AU - Chenevix-Trench, Georgia
AU - Clarke, Christine L.
AU - Couch, Fergus J.
AU - Cox, Angela
AU - Cross, Simon S.
AU - Czene, Kamila
AU - Dai, James Y.
AU - Earp, H. Shelton
AU - Ekici, Arif B.
AU - Olson, Janet E.
AU - Polley, Eric C.
AU - Ruddy, Kathryn J.
AU - Vachon, Celine M.
AU - Winham, Stacey J.
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/djaa056
DO - 10.1093/jnci/djaa056
M3 - Article
C2 - 32359158
AN - SCOPUS:85102687861
SN - 0027-8874
VL - 113
SP - 329
EP - 337
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 3
ER -