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

Kapoor, Pooja Middha ; Mavaddat, Nasim ; Choudhury, Parichoy Pal ; Wilcox, Amber N ; Lindström, Sara LU ; Behrens, Sabine ; Michailidou, Kyriaki ; Dennis, Joe ; Bolla, Manjeet K and Wang, Qin , et al. (2020) In Journal of the National Cancer Institute
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... (More)

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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publishing date
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Contribution to journal
publication status
epub
subject
in
Journal of the National Cancer Institute
publisher
Oxford University Press
external identifiers
  • pmid:32359158
ISSN
1460-2105
DOI
10.1093/jnci/djaa056
language
English
LU publication?
no
additional info
© The Author(s) 2020. Published by Oxford University Press.
id
549a6a05-7fc4-45b3-b843-e87f89a4de46
date added to LUP
2020-05-08 14:34:51
date last changed
2020-05-20 15:39:04
@article{549a6a05-7fc4-45b3-b843-e87f89a4de46,
  abstract     = {<p>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.</p>},
  author       = {Kapoor, Pooja Middha and Mavaddat, Nasim and Choudhury, Parichoy Pal and Wilcox, Amber N and Lindström, Sara and Behrens, Sabine and Michailidou, Kyriaki and Dennis, Joe and Bolla, Manjeet K and Wang, Qin and Jung, Audrey and Abu-Ful, Zomoroda and Ahearn, Thomas and Andrulis, Irene L and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J and Auer, Paul L and Freeman, Laura E Beane and Becher, Heiko and Beckmann, Matthias W and Beeghly-Fadiel, Alicia and Benitez, Javier and Bernstein, Leslie and Bojesen, Stig E and Brauch, Hiltrud and Brenner, Hermann and Brüning, Thomas and Cai, Qiuyin and Campa, Daniele and Canzian, Federico and Carracedo, Angel and Carter, Brian D and Castelao, Jose E and Chanock, Stephen J and Chatterjee, Nilanjan and Chenevix-Trench, Georgia and Clarke, Christine L and Couch, Fergus J and Cox, Angela and Cross, Simon S and Czene, Kamila and Dai, James Y and Earp, H Shelton and Ekici, Arif B and Eliassen, A Heather and Eriksson, Mikael and Evans, D Gareth and Fasching, Peter A and Hall, Per and Chang-Claude, Jenny},
  issn         = {1460-2105},
  language     = {eng},
  month        = {05},
  publisher    = {Oxford University Press},
  series       = {Journal of the National Cancer Institute},
  title        = {Combined associations of a polygenic risk score and classical risk factors with breast cancer risk},
  url          = {http://dx.doi.org/10.1093/jnci/djaa056},
  doi          = {10.1093/jnci/djaa056},
  year         = {2020},
}