Journal Article

DKFZ-2018-00557

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium.

Rudolph, A. (First author)DKFZ* ; Song, M. ; Brook, M. N. ; Milne, R. L. ; Mavaddat, N. ; Michailidou, K. ; Bolla, M. K. ; Wang, Q. ; Dennis, J. ; Wilcox, A. N. ; Hopper, J. L. ; Southey, M. C. ; Keeman, R. ; Fasching, P. A. ; Beckmann, M. W. ; Gago-Dominguez, M. ; Castelao, J. E. ; Guénel, P. ; Truong, T. ; Bojesen, S. E. ; Flyger, H. ; Brenner, H.DKFZ* ; Arndt, V.DKFZ* ; Brauch, H.DKFZ* ; Brüning, T. ; Mannermaa, A. ; Kosma, V.-M. ; Lambrechts, D. ; Keupers, M. ; Couch, F. J. ; Vachon, C. ; Giles, G. G. ; MacInnis, R. J. ; Figueroa, J. ; Brinton, L. ; Czene, K. ; Brand, J. S. ; Gabrielson, M. ; Humphreys, K. ; Cox, A. ; Cross, S. S. ; Dunning, A. M. ; Orr, N. ; Swerdlow, A. ; Hall, P. ; Pharoah, P. D. P. ; Schmidt, M. K. ; Easton, D. F. ; Chatterjee, N. ; Chang-Claude, J. (Last author)DKFZ* ; García-Closas, M.

2018
Oxford Univ. Press Oxford

This record in other databases:  

Please use a persistent id in citations: doi:10.1093/ije/dyx242

Abstract: Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors.Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status.The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction = 0.009), adult height (P-interaction = 0.025) and current use of combined MHT (P-interaction = 0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P = 0.013 for global and 0.18 for tail-based tests).The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (G110)
4. DKTK Heidelberg (L101)
5. DKTK Tübingen (L801)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2018

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Database coverage:
; Allianz-Lizenz / DFG ; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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