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.
|Journal||npj Breast Cancer|
|State||Published - Dec 1 2020|
Bibliographical noteFunding Information:
This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the US National Cancer Institute. Breast Cancer Research Stamp Funds (awarded to M.E. Sherman and L.A. Brinton) and cooperative agreement U01CA70013 (P.M. Vacek, D.L. Weaver) from the National Cancer Institute funded some of the data collection for this study. The efforts of Drs. Sprague, Vacek, and Weaver were supported in part by cooperative agreement U01 CA196383 from the National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Data from the Susan G. Komen Tissue Bank at the IU Simon Cancer Center were used in this study. We thank contributors, including Indiana University who collected data used in this study, as well as donors and their families, whose help and participation made this work possible.
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Pharmacology (medical)