Journal Article

DKFZ-2024-02085

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Polygenic risk scores stratify breast cancer risk among women with benign breast disease.

Sherman, M. E. ; Winham, S. J. ; Vierkant, R. A. ; Mccauley, B. M. ; Scott, C. G. ; Schrup, S. ; Gaudet, M. M. ; Troester, M. A. ; Pruthi, S. ; Radisky, D. C. ; Degnim, A. C. ; Couch, F. J. ; Bolla, M. K. ; Wang, Q. ; Dennis, J. ; Michailidou, K. ; Guenel, P. ; Truong, T. ; Chang-Claude, J.DKFZ* ; Obi, N. ; Aronson, K. J. ; Murphy, R. ; Garcia-Closas, M. ; Chanock, S. ; Ahearn, T. ; Yang, X. ; Dunning, A. M. ; Mavaddat, N. ; Pharoah, P. D. P. ; Easton, D. F. ; Vachon, C. M.

2025
Oxford Univ. Press Oxford

Abstract: Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients. We assessed whether a 313-SNP polygenic risk score (PRS) stratifies risk of BBD patients.We pooled data from five Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6,706 cases and 8,488 controls. Using logistic regression, we estimated BC risk associations by self-reported BBD history and strata of PRS, with median PRS category among women without BBD as the referent. We assessed interactions and mediation of BBD and PRS with BC risk.BBD history was associated with increased BC risk (OR = 1.48, 95% CI: 1.37-1.60; p < .001). PRS increased BC risk, irrespective of BBD history (p-interaction = 0.48), with minimal evidence of mediation of either factor by the other. Women with BBD and PRS in the highest tertile had over 2-fold increased odds of BC (OR = 2.73, 95% CI: 2.41-3.09) and those with BBD and PRS in the lowest tertile experienced reduced BC risk (OR = 0.79, 95% CI: 0.70-0.91), compared to the reference group. Women with BBD and PRS in the highest decile had a 3.7- fold increase (95% CI: 3.00-4.61) compared to those with median PRS without BBD.BC risks are elevated among women with BBD and increase progressively with PRS, suggesting that optimal combinations of these factors may improve risk stratification.

Note: 2025 Mar 1;117(3):456-464

---

Contributing Institute(s):

1. Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2024

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---