While 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. A 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. Sphingomyelin (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. We 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.

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绝经前女性乳房 X 光密度的生物标志物

虽然乳房 X 光检查密度是乳腺癌的最强风险因素之一，但对其决定因素知之甚少，尤其是在年轻女性中。我们应用靶向代谢组学来鉴定与绝经前女性乳房 X 线照相密度特别相关的循环代谢物。然后，我们旨在确定这些生物标志物的潜在相关性，以指导未来对乳房 X 光密度的潜在可修改决定因素的研究。通过串联液相色谱/质谱法对来自墨西哥教师队列的 573 名绝经前参与者的血浆样本进行了总共 132 种代谢物（酰基肉碱、氨基酸、生物胺、甘油磷脂、鞘脂、己糖）的测量。使用线性回归模型评估代谢物和百分比乳房 X 线照相密度之间的关联，调整乳腺癌风险因素并考虑多项测试。与乳房 X 线照相密度百分比相关的代谢物的平均浓度是在几种生活方式和代谢因素的水平上估计的。鞘磷脂 (SM) C16:1 和磷脂酰胆碱 (PC) ae C30:2 在多次测试校正后与乳房 X 线照相密度百分比呈负相关。仅在体重指数 (BMI) 低于中位数 (27.4) 的女性中观察到 SM C16:1 和 BMI 高于中位数的女性中 PC ae C30:2 的线性趋势。SM C16:1 和 PC ae C30:2 浓度与胆固醇（总胆固醇和 HDL）呈正相关，与代谢综合征成分的数量呈负相关。我们确定了与年轻女性乳房 X 光密度相关的新生物标志物。