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Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast

Authors
  • Bodelon, Clara1
  • Oh, Hannah1, 2
  • Derkach, Andriy1
  • Sampson, Joshua N.1
  • Sprague, Brian L.3
  • Vacek, Pamela3
  • Weaver, Donald L.3
  • Fan, Shaoqi1
  • Palakal, Maya1
  • Papathomas, Daphne1
  • Xiang, Jackie1
  • Patel, Deesha A.1
  • Linville, Laura1
  • Clare, Susan E.4
  • Visscher, Daniel W.5
  • Mies, Carolyn6
  • Hewitt, Stephen M.7
  • Brinton, Louise A.1
  • Storniolo, Anna Maria V.8
  • He, Chunyan9, 10
  • And 4 more
  • 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA , Bethesda (United States)
  • 2 Division of Health Policy and Management, College of Health Sciences, Korea University, Seoul, Korea , Seoul (South Korea)
  • 3 University of Vermont College of Medicine and Vermont Cancer Center, Burlington, VT, USA , Burlington (United States)
  • 4 Feinberg School of Medicine, Northwestern University, Chicago, IL, USA , Chicago (United States)
  • 5 Mayo Clinic, Rochester, MN, USA , Rochester (United States)
  • 6 University of Pennsylvania, Philadelphia, PA, USA , Philadelphia (United States)
  • 7 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA , Bethesda (United States)
  • 8 Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, IN, USA , Indianapolis (United States)
  • 9 Division of Medical Oncology, College of Medicine, University of Kentucky, Lexington, KY, USA , Lexington (United States)
  • 10 University of Kentucky, Lexington, KY, USA , Lexington (United States)
  • 11 Usher Institute of Population Health Sciences and Informatics and Cancer Research UK Edinburgh Centre, University of Edinburgh, Edinburgh, UK , Edinburgh (United Kingdom)
Type
Published Article
Journal
npj Breast Cancer
Publisher
Nature Publishing Group UK
Publication Date
Sep 07, 2020
Volume
6
Issue
1
Identifiers
DOI: 10.1038/s41523-020-00184-7
Source
Springer Nature
License
Green

Abstract

Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer. Among 1398 women without breast cancer, higher values of the PRS were significantly associated with higher TDLU counts (P = 0.004), but not with acini counts (P = 0.808), in histologically normal tissue samples from donors and diagnostic BBD biopsies. Mediation analysis indicated that TDLU counts may explain a modest proportion (≤10%) of the association of the 313-variant PRS with breast cancer risk. These findings suggest that TDLU involution might be an intermediate step in the association between common genetic variation and breast cancer risk.

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