High-Density Lipoprotein Cholesterol, Obesity, and Mammographic Density in Korean Women: The Healthy Twin Study

Background: High-density lipoprotein cholesterol (HDL-C) is reported to be associated with breast cancer risk. To better understand this association, we examined the relationship between HDL-C and mammographic density, a putative intermediate risk factor for breast cancer. Methods: The study subjects were 711 Korean women from the Healthy Twin study. Lipid parameters were assayed enzymatically in fresh sera, and percent dense area (PDA) and absolute dense area were measured from digital mammograms using a computer-assisted method. Results: PDA was positively associated with HDL-C in both premenopausal and postmenopausal women in a multivariable-adjusted linear mixed model, but the association did not persist when the model was additionally adjusted for body mass index (BMI). BMI was inversely associated with PDA, and this association did not change after additional adjustment for any lipid parameter. Multivariable-adjusted analysis showed that there were significant additive genetic cross-trait correlations between PDA and both HDL-C (coefficient, 0.175) and triglyceride (coefficient, -0.262). However, those correlations disappeared after additional adjustment for BMI. Conclusions: HDL-C alone is unlikely to increase the risk of breast cancer in Korean women, particularly through changes in breast parenchyma that are apparent in mammographic density. BMI should be included in studies using analytical models where mammographic density is used as an intermediate risk factor for breast cancer.