Mammographic Density and Expression of the Genes Involved in the de novo Cholesterol Biosynthesis Mammographic density and cholesterol biosynthesis

Danila Coradini (1)
(1) Laboratory of Medical Statistics and Biometry, Department of Clinical Sciences and Community Health, Campus Cascina Rosa, University of Milan, Italy, Italy


Background: This in silico study investigated the association between the local biosynthesis of cholesterol and mammographic density, the major risk of developing breast cancer, as a function of the three cellular components of breast tissue (epithelium, fatty, and non-fatty stroma).

Methods: The study compared the expression of 7 genes (HMGCR, FDPS, FDFT1, GGPS1, SQLE, LSS, and SREBF2) involved in the de novo cholesterol biosynthesis, first, according to the radiological density (dense vs. non-dense breast) and, then, according to the cellular components of breast tissue, regardless the radiological classification.

Results: HMGCR, SQLE, and SBREF2 were significantly more expressed in radiologically dense than in non-dense breasts (-1.70 vs. -1.41, P=0.0028; -1.20 vs. -1.11, P=0.0501; -3.63 vs. -3.31 P=0.0003; -0.92 vs. -0.76, P=0.0271, respectively). When the samples were reclassified based on their cellular components as highly fatty and highly non-fatty, HMGCR, SQLE, and SBREF2 were significantly more expressed in highly non-fatty samples (-1.48 vs. -1.94, P<0.0001; -3.39 vs. -4.18, P<0.0001; -0.77 vs. -0.94, P=0.0103, respectively) whereas LSS was overexpressed in high fatty ones (0.28 vs. -0.60, P<0.0001). Besides, while in the highly non-fatty subgroup SREBF2 was positively associated with both HMGCR (r=0.53, P<0.0001) and SQLE (r=0.73, P<0.0001), in the highly fatty subgroup these positive correlations disappeared (SREBF2*HMGCR: r=-0.19, P=0.3026) or substantially decreased (SREBF2*SQLE: r=0.41, P=0.0173).

Conclusion: Findings provide a compelling biological explanation for the clinical evidence that women with radiologically dense breasts are at a higher risk of developing cancer compared to those with non-dense breasts because of the prevalence of non-fatty tissue, where the altered expression of genes leading to an increased cholesterol production, can contribute to the transformation of epithelial cells, and support the use of mammographic density as a reliable surrogate marker to identify women who may benefit from a preventive treatment aimed at reducing cholesterol production.

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Danila Coradini (Primary Contact)
Coradini D. Mammographic Density and Expression of the Genes Involved in the de novo Cholesterol Biosynthesis: Mammographic density and cholesterol biosynthesis. Arch Breast Cancer [Internet]. [cited 2024 Jul. 14];11(3). Available from:

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