Abstract
Background: Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important since the mechanisms through which they are associated with breast cancer are not well known.
Methods: Mammographic screening history and detailed questionnaire data for 56,820 women from the KARMA prospective cohort study were used. The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC – cm2/year) were estimated using 1,940 sister pairs. We investigated the association between a genetic predisposition to breast cancer and mammographic features, among women with family history of breast cancer information (N=49,674) and a polygenic risk score (PRS, N=9,365).
Results: Heritability was estimated at 58% (95% CI: 48%, 67%) for MD, 23% (2%, 45%) for microcalcifications, and 13% (1%, 25%) for masses. The estimated heritability for MDC was essentially null (2%, 95% CI: -8%, 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction.
Conclusions: We confirmed previous findings of heritability in MD, and also found heritability of the number of microcalcifications and masses at baseline. Since these features are associated with breast cancer risk, and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer.
