Prediagnostic circulating metabolites in female breast cancer cases with low and high mammographic breast density.
Prediagnostic circulating metabolites in female breast cancer cases with low and high mammographic breast density.
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DOI：
10.1038/s41598-021-92508-1
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发表时间：
2021-06-22
影响因子：
4.6
通讯作者：
Masala G
中科院分区：
文献类型：
--
作者：
Bendinelli B;Vignoli A;Palli D;Assedi M;Ambrogetti D;Luchinat C;Caini S;Saieva C;Turano P;Masala G
乳腺摄影乳腺密度（MBD）是乳腺癌（BC）的一个强独立危险因素。我们在EPIC佛罗伦萨队列中设计了一项配对病例-病例研究，以评估在随访期间发生BC的高MBD与低MBD女性的诊断前代谢组学特征与BC风险之间的可能关联。进行病例-病例设计，其中100例低MBD（MBD ≤ 25%）和100例高MDB BC病例（MBD > 50%）。匹配变量包括年龄、年份和乳房X线检查类型。1H NMR代谢组学谱可用于87个完整的病例-病例集。条件Logistic分析显示血清丙氨酸、亮氨酸、酪氨酸、缬氨酸、乳酸、甘油三酯、甘油三酯、脂质主要组分和11种VLDL脂质亚组分水平与高MBD病例呈负相关。醋酸与高MBD病例直接相关。在调整混杂变量的模型中，酪氨酸与高MBD病例呈负相关，而游离胆固醇的3个VLDL亚组分与高MBD病例直接相关。途径分析表明，“苯丙氨酸，酪氨酸和色氨酸途径”出现并持续应用FDR程序后。监督OPLS-DA分析揭示了轻微的，但显着的分离高和低MBD的情况下。这项病例-病例研究表明，诊断前酪氨酸水平可能在调节高MBD女性与低MBD女性的BC风险中发挥作用。此外，两组患者的其他代谢物的诊断前浓度以及代谢组学指纹也存在一些差异。
Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We designed a matched case–case study in the EPIC Florence cohort, to evaluate possible associations between the pre-diagnostic metabolomic profile and the risk of BC in high- versus low-MBD women who developed BC during the follow-up. A case–case design with 100 low-MBD (MBD ≤ 25%) and 100 high-MDB BC cases (MBD > 50%) was performed. Matching variables included age, year and type of mammographic examination. 1H NMR metabolomic spectra were available for 87 complete case–case sets. The conditional logistic analyses showed an inverse association between serum levels of alanine, leucine, tyrosine, valine, lactic acid, pyruvic acid, triglycerides lipid main fraction and 11 VLDL lipid subfractions and high-MBD cases. Acetic acid was directly associated with high-MBD cases. In models adjusted for confounding variables, tyrosine remained inversely associated with high-MBD cases while 3 VLDL subfractions of free cholesterol emerged as directly associated with high-MBD cases. A pathway analysis showed that the “phenylalanine, tyrosine and tryptophan pathway” emerged and persisted after applying the FDR procedure. The supervised OPLS-DA analysis revealed a slight but significant separation between high- and low-MBD cases. This case–case study suggested a possible role for pre-diagnostic levels of tyrosine in modulating the risk of BC in high- versus low-MBD women. Moreover, some differences emerged in the pre-diagnostic concentration of other metabolites as well in the metabolomic fingerprints among the two groups of patients.
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影响因子：
2.6
作者：
Conroy, Shannon M.;Pagano, Ian;Maskarinec, Gertraud
通讯作者：
Maskarinec, Gertraud
影响因子：
6.1
作者：
Bi X;Henry CJ
通讯作者：
Henry CJ
影响因子：
7.7
作者：
Lecuyer, Lucie;Bala, Agnes Victor;Touvier, Mathilde
通讯作者：
Touvier, Mathilde
影响因子：
11.5
作者：
Hart, Christopher D.;Vignoli, Alessia;Di Leo, Angelo
通讯作者：
Di Leo, Angelo
影响因子：
2.9
作者：
Bai, Jie;Zhang, Xiaoyu;Wang, Zunyi
通讯作者：
Wang, Zunyi