乳がんリスクを予測する代謝マーカーの特定(Metabolic Markers May Predict Breast Cancer in High-Risk Women)

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2025-09-22 コロンビア大学

コロンビア大学メールマン公衆衛生大学院の研究で、代謝マーカーが高リスク女性の乳がん発症を予測できる可能性が示された。乳がん家族歴を持つ女性110人(発症40人・非発症70人)を対象にメタボローム解析を実施し、8種類の代謝物が発症リスクと有意に関連した。これらの代謝情報を既存リスク予測モデルに統合すると、予測精度が66%から83%へ向上。特に、動物実験で乳腺腫瘍を誘発する化学物質「1,3-ジブチル-1-ニトロソウレア」との関連を初めて人で確認した。食事や環境曝露など代謝経路を介した乳がん発症要因の解明に新たな道を開く成果である。

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血漿メタボロミクスプロファイルと乳がんリスク Plasma metabolomics profiles and breast cancer risk

Hui-Chen Wu,Yunjia Lai,Yuyan Liao,Maya Deyssenroth,Gary W. Miller,Regina M. Santella & Mary Beth Terry
Breast Cancer Research  Published:09 October 2024
DOI:https://doi.org/10.1186/s13058-024-01896-5

乳がんリスクを予測する代謝マーカーの特定(Metabolic Markers May Predict Breast Cancer in High-Risk Women)

Abstract

Background

Breast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors.

Methods

We conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features.

Results

We found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%.

Conclusions

If replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.

医療・健康
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