Combined associations of a polygenic risk score and classical risk factors with breast cancer risk

Pooja Middha Kapoor; Nasim Mavaddat; Parichoy Pal Choudhury; Amber N Wilcox; Sara Lindström; Sabine Behrens; Kyriaki Michailidou; Joe Dennis; Manjeet K Bolla; Qin Wang; Audrey Jung; Zomoroda Abu-Ful; Thomas Ahearn; Irene L Andrulis; Hoda Anton-Culver; Volker Arndt; Kristan J Aronson; Paul L Auer; Laura E Beane Freeman; Heiko Becher; Matthias W Beckmann; Alicia Beeghly-Fadiel; Javier Benitez; Leslie Bernstein; Stig E Bojesen; Hiltrud Brauch; Hermann Brenner; Thomas Brüning; Qiuyin Cai; Daniele Campa; Federico Canzian; Angel Carracedo; Brian D Carter; Jose E Castelao; Stephen J Chanock; Nilanjan Chatterjee; Georgia Chenevix-Trench; Christine L Clarke; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; James Y Dai; H Shelton Earp; Arif B Ekici; A Heather Eliassen; Mikael Eriksson; David J Hunter; Michael E Jones; Nick Orr; ABCTB Investigators

doi:10.1093/jnci/djaa056

Combined associations of a polygenic risk score and classical risk factors with breast cancer risk

Pooja Middha Kapoor, Nasim Mavaddat, Parichoy Pal Choudhury, Amber N Wilcox, Sara Lindström, Sabine Behrens, Kyriaki Michailidou, Joe Dennis, Manjeet K Bolla, Qin Wang, Audrey Jung, Zomoroda Abu-Ful, Thomas Ahearn, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J Aronson, Paul L Auer, Laura E Beane Freeman, Heiko BecherMatthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Leslie Bernstein, Stig E Bojesen, Hiltrud Brauch, Hermann Brenner, Thomas Brüning, Qiuyin Cai, Daniele Campa, Federico Canzian, Angel Carracedo, Brian D Carter, Jose E Castelao, Stephen J Chanock, Nilanjan Chatterjee, Georgia Chenevix-Trench, Christine L Clarke, Fergus J Couch, Angela Cox, Simon S Cross, Kamila Czene, James Y Dai, H Shelton Earp, Arif B Ekici, A Heather Eliassen, Mikael Eriksson, David J Hunter, Michael E Jones, Nick Orr, ABCTB Investigators

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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.

Original language	English
Journal	Journal of the National Cancer Institute
Early online date	02 May 2020
DOIs	https://doi.org/10.1093/jnci/djaa056
Publication status	Early online date - 02 May 2020

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10.1093/jnci/djaa056Licence: CC BY

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk
Copyright 2020 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.33 MBLicence: CC BY

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Kapoor, P. M., Mavaddat, N., Choudhury, P. P., Wilcox, A. N., Lindström, S., Behrens, S., Michailidou, K., Dennis, J., Bolla, M. K., Wang, Q., Jung, A., Abu-Ful, Z., Ahearn, T., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Auer, P. L., Freeman, L. E. B., ... ABCTB Investigators (2020). Combined associations of a polygenic risk score and classical risk factors with breast cancer risk. Journal of the National Cancer Institute. Advance online publication. https://doi.org/10.1093/jnci/djaa056

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title = "Combined associations of a polygenic risk score and classical risk factors with breast cancer risk",

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.",

author = "Kapoor, {Pooja Middha} and Nasim Mavaddat and Choudhury, {Parichoy Pal} and Wilcox, {Amber N} and Sara Lindstr{\"o}m and Sabine Behrens and Kyriaki Michailidou and Joe Dennis and Bolla, {Manjeet K} and Qin Wang and Audrey Jung and Zomoroda Abu-Ful and Thomas Ahearn and Andrulis, {Irene L} and Hoda Anton-Culver and Volker Arndt and Aronson, {Kristan J} and Auer, {Paul L} and Freeman, {Laura E Beane} and Heiko Becher and Beckmann, {Matthias W} and Alicia Beeghly-Fadiel and Javier Benitez and Leslie Bernstein and Bojesen, {Stig E} and Hiltrud Brauch and Hermann Brenner and Thomas Br{\"u}ning and Qiuyin Cai and Daniele Campa and Federico Canzian and Angel Carracedo and Carter, {Brian D} and Castelao, {Jose E} and Chanock, {Stephen J} and Nilanjan Chatterjee and Georgia Chenevix-Trench and Clarke, {Christine L} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Dai, {James Y} and Earp, {H Shelton} and Ekici, {Arif B} and Eliassen, {A Heather} and Mikael Eriksson and Hunter, {David J} and Jones, {Michael E} and Nick Orr and {ABCTB Investigators}",

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Kapoor, PM, Mavaddat, N, Choudhury, PP, Wilcox, AN, Lindström, S, Behrens, S, Michailidou, K, Dennis, J, Bolla, MK, Wang, Q, Jung, A, Abu-Ful, Z, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Auer, PL, Freeman, LEB, Becher, H, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bernstein, L, Bojesen, SE, Brauch, H, Brenner, H, Brüning, T, Cai, Q, Campa, D, Canzian, F, Carracedo, A, Carter, BD, Castelao, JE, Chanock, SJ, Chatterjee, N, Chenevix-Trench, G, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Dai, JY, Earp, HS, Ekici, AB, Eliassen, AH, Eriksson, M, Hunter, DJ, Jones, ME, Orr, N & ABCTB Investigators 2020, 'Combined associations of a polygenic risk score and classical risk factors with breast cancer risk', Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djaa056

TY - JOUR

T1 - Combined associations of a polygenic risk score and classical risk factors with breast cancer risk

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 - Eliassen, A Heather

AU - Eriksson, Mikael

AU - Hunter, David J

AU - Jones, Michael E

AU - Orr, Nick

AU - ABCTB Investigators

PY - 2020/5/2

Y1 - 2020/5/2

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.

U2 - 10.1093/jnci/djaa056

DO - 10.1093/jnci/djaa056

M3 - Article

C2 - 32359158

SN - 0027-8874

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

ER -

Combined associations of a polygenic risk score and classical risk factors with breast cancer risk

Abstract

Bibliographical note

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