主要针对绝经前女性的循环代谢组学特征与乳腺癌发病率的前瞻性研究。

Prospective study of circulating metabolomic profiles and breast cancer incidence among predominantly premenopausal women.

作者信息

Wang Tengteng, Zeleznik Oana A, McGee Emma E, Brantley Kristen D, Balasubramanian Raji, Rosner Bernard A, Willett Walter C, Avila-Pacheco Julian, Clish Clary B, Eliassen A Heather

机构信息

Department of Medicine, Division of Medical Oncology, Section of Cancer Epidemiology and Health Outcomes, Rutgers Robert Wood Johnson Medical School, Rutgers Cancer Institute, New Brunswick, NJ, USA.

Cancer Prevention and Control Program, Rutgers Cancer Institute, New Brunswick, NJ, USA.

出版信息

Br J Cancer. 2025 Sep 4. doi: 10.1038/s41416-025-03159-2.

DOI:10.1038/s41416-025-03159-2

PMID:40908295

Abstract

BACKGROUND

Associations between premenopausal plasma metabolites and breast cancer incidence are largely unknown.

METHODS

We conducted a prospective, matched case-control study in which we measured pre-diagnostic metabolomic profiles among predominantly premenopausal women in the Nurses' Health Study II (n = 2010). Lipids, carbohydrates, and organic acid-related metabolites (n = 218) were profiled via liquid chromatography-tandem mass spectrometry. Conditional logistic regression was used to estimate odds ratios (OR) for associations between individual metabolites and breast cancer incidence. Associations with metabolite groups were assessed using metabolite set enrichment analysis (MSEA).

RESULTS

Six individual lipid-related metabolites were nominally associated with breast cancer incidence (taurodeoxycholate [OR for per 1 standard deviation increase in metabolite level = 1.15, 95% CI = 1.04-1.28]; C16:1 cholesteryl ester [OR = 0.88, 95% CI = 0.79-0.97]; three phosphocholine (PC)-related metabolites, C34:1 PC [OR = 0.87, 95% CI = 0.78-0.98], C34:3 PC [OR = 0.88, 95% CI = 0.79-0.98], C32:1 PC [OR = 0.88, 95% CI = 0.79-0.98]; indoxyl sulfate [OR = 0.90, 95% CI = 0.82-1.00]). In MSEA analyses, triglycerides (TAGs) with <3 double bonds (normalized enrichment score (NES) = -2.54) and PCs (NES = -2.12) were inversely associated with breast cancer incidence overall and across subgroups. Phosphatidylethanolamine (PE) plasmalogens (NES = 1.83) and PC plasmalogens (NES = 2.23) were positively associated with breast cancer incidence.

CONCLUSIONS

Premenopausal plasma TAGs, PCs, and plasmalogen metabolites were associated with breast cancer incidence. Further validation in independent cohorts is warranted.

摘要

背景

绝经前血浆代谢物与乳腺癌发病率之间的关联在很大程度上尚不清楚。

方法

我们进行了一项前瞻性、匹配病例对照研究，在护士健康研究II（n = 2010）中，测量了主要为绝经前女性的诊断前代谢组学特征。通过液相色谱 - 串联质谱法对脂质、碳水化合物和有机酸相关代谢物（n = 218）进行了分析。使用条件逻辑回归估计个体代谢物与乳腺癌发病率之间关联的比值比（OR）。使用代谢物集富集分析（MSEA）评估与代谢物组的关联。

结果

六种与脂质相关的个体代谢物与乳腺癌发病率名义上相关（牛磺去氧胆酸盐[代谢物水平每增加1个标准差的OR = 1.15，95%CI = 1.04 - 1.28]；C16:1胆固醇酯[OR = 0.88，95%CI = 0.79 - 0.97]；三种与磷酸胆碱（PC）相关的代谢物，C34:1 PC[OR = 0.87，95%CI = 0.78 - 0.98]，C34:3 PC[OR = 0.88，95%CI = 0.79 - 0.98]，C32:1 PC[OR = 0.88，95%CI = 0.79 - 0.98]；硫酸吲哚酚[OR = 0.90，95%CI = 0.82 - 1.00]）。在MSEA分析中，双键数<3的甘油三酯（TAGs）（标准化富集分数（NES）= -2.54）和PCs（NES = -2.12）与总体及各亚组的乳腺癌发病率呈负相关。磷脂酰乙醇胺（PE）缩醛磷脂（NES = 1.83）和PC缩醛磷脂（NES = 2.23）与乳腺癌发病率呈正相关。