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Familial Aspects of Mammographic Density Measures Associated with Breast Cancer Risk.

Published version
Peer-reviewed

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Type

Article

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Authors

Nguyen, Tuong L 
Dowty, James G 

Abstract

Cumulus, Cumulus-percent, Altocumulus, Cirrocumulus, and Cumulus-white are mammogram risk scores (MRSs) for breast cancer based on mammographic density defined in effect by different levels of pixel brightness and adjusted for age and body mass index. We measured these MRS from digitized film mammograms for 593 monozygotic (MZ) and 326 dizygotic (DZ) female twin pairs and 1592 of their sisters. We estimated the correlations in relatives (r) and the proportion of variance due to genetic factors (heritability) using the software FISHER and predicted the familial risk ratio (FRR) associated with each MRS. The ρ estimates ranged from: 0.41 to 0.60 (standard error [SE] 0.02) for MZ pairs, 0.16 to 0.26 (SE 0.05) for DZ pairs, and 0.19 to 0.29 (SE 0.02) for sister pairs (including pairs of a twin and her non-twin sister), respectively. Heritability estimates were 39% to 69% under the classic twin model and 36% to 56% when allowing for shared non-genetic factors specific to MZ pairs. The FRRs were 1.08 to 1.17. These MRSs are substantially familial, due mostly to genetic factors that explain one-quarter to one-half as much of the familial aggregation of breast cancer that is explained by the current best polygenic risk score.

Description

Keywords

Heritability, Breast cancer, Mammographic Density, Opera, Cumulus, Cirrocumulus, Familial Risk Ratio, Mammogram Risk Score

Journal Title

Cancers (Basel)

Conference Name

Journal ISSN

2072-6694
2072-6694

Volume Title

14

Publisher

MDPI AG
Sponsorship
National Breast Cancer Foundation (ECF-17-001)
Cancer Council Victoria (AF7305)
National Health and Medical Research Council (APP809195)
Victorian Cancer Agency (ECRF19020)
NIH HHS (R01CA159868)
National Institutes of Health (R01CA159868)