Abstract
BackgroundWhile mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density.MethodsA total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers’ Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors.ResultsSphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components.ConclusionsWe identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.
Highlights
While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women
All variables previously listed as covariates in the main analyses were examined using similar categories or tertiles for variables initially included as continuous. In addition to these variables, we investigated waist circumference, hip circumference, high blood pressure, circulating leptin, adiponectin, leptin/adiponectin ratio, Insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), C-peptide, C reactive protein (CRP), total cholesterol, High density lipoprotein (HDL) cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, glucose, and number of criteria for determination of metabolic syndrome
Moderate positive correlations were observed among amino acids, acylcarnitines, and phosphatidylcholines and were stronger among lysophosphatidylcholines and sphingomyelins (Supplementary Figure 1)
Summary
While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. Women with a high mammographic density have an increased risk for breast cancer, that is estimated to be 4.6 times higher for mammographic density ≥ 75% compared with < 5% [10]. The direct association between high mammographic density and risk of breast cancer has been observed both in post- and premenopausal women [11]. Since premenopausal women are not targeted in existing mammography screening programs, it is not possible to identify premenopausal women with a high mammographic density, at increased risk for breast cancer. The identification of specific biomarkers for high mammographic density may represent a valuable alternative to mammography to identify women at higher breast cancer risk
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