Exploring metabolomics for colorectal cancer risk prediction: evidence from the UK Biobank and ESTHER cohorts.

IF 7 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Teresa Seum, Rafael Cardoso, Joshua Stevenson-Hoare, Bernd Holleczek, Ben Schöttker, Michael Hoffmeister, Hermann Brenner
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引用次数: 0

Abstract

Background: While metabolic pathway alterations are linked to colorectal cancer (CRC), the predictive value of pre-diagnostic metabolomic profiling in CRC risk assessment remains to be clarified. This study evaluated the predictive performance of a metabolomics risk panel (MRP) both independently and in combination with established risk factors.

Methods: We derived, internally validated (IV), and externally validated (EV) a metabolomics risk panel (MRP) for CRC from data of the UK Biobank (UKB) and the German ESTHER cohort. Baseline blood samples were assessed for 249 metabolites using nuclear magnetic resonance spectroscopy analysis. We applied LASSO Cox proportional hazards regression to identify metabolites for inclusion in the MRP and evaluated the model performance using the concordance index (C-index). We compared the performance of the MRP to an environmental risk panel (ERP; sex, age, body mass index, smoking status, and alcohol consumption) and a genetic risk panel (GRP; polygenic risk score).

Results: The study included 154,892 participants of the UKB cohort (mean age at baseline 54.5 years; 55.5% female) with 1879 incident CRC and 3242 participants of the ESTHER cohort (mean age 61.5 years; 52.2% female) with 103 CRC cases. Twenty-three metabolites, primarily amino acid and lipid-related metabolites, were selected for the MRP, showing moderate predictive performance (C-index 0.60 [IV] and 0.54 [EV]). The ERP and GRP showed superior performance, with C-index values of 0.73 (IV) and 0.69 (EV). Adding the MRP to these risk models did not change the C-indices in both cohorts.

Conclusions: Genetic and environmental risk information provided strong predictive accuracy for CRC risk, with no improvements from adding metabolomics data. These findings suggest that metabolomics data may have limited impact on enhancing established CRC risk models in clinical practice.

探索结肠直肠癌风险预测的代谢组学:来自英国生物银行和ESTHER队列的证据。
背景:虽然代谢途径改变与结直肠癌(CRC)有关,但诊断前代谢组学分析在结直肠癌风险评估中的预测价值仍有待阐明。本研究评估了代谢组学风险面板(MRP)的预测性能,包括独立的和与既定风险因素的组合。方法:我们从英国生物银行(UKB)和德国ESTHER队列的数据中导出了CRC的代谢组学风险面板(MRP),内部验证(IV)和外部验证(EV)。基线血液样本使用核磁共振波谱分析评估249种代谢物。我们使用LASSO Cox比例风险回归来确定纳入MRP的代谢物,并使用一致性指数(C-index)评估模型的性能。我们将MRP的绩效与环境风险面板(ERP;性别、年龄、体重指数、吸烟状况和饮酒)和遗传风险小组(GRP;多基因风险评分)。结果:该研究纳入了154,892名UKB队列参与者(基线时平均年龄54.5岁;55.5%为女性),有1879例CRC事件和3242例ESTHER队列参与者(平均年龄61.5岁;52.2%女性),103例结直肠癌。MRP选择了23种代谢物,主要是氨基酸和脂质相关代谢物,具有中等的预测性能(C-index为0.60 [IV]和0.54 [EV])。ERP和GRP的c指数值分别为0.73 (IV)和0.69 (EV)。在这些风险模型中加入MRP并没有改变两个队列的c指数。结论:遗传和环境风险信息对结直肠癌风险提供了很强的预测准确性,添加代谢组学数据没有改善。这些发现表明,代谢组学数据在临床实践中对增强已建立的结直肠癌风险模型的影响可能有限。
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来源期刊
BMC Medicine
BMC Medicine 医学-医学:内科
CiteScore
13.10
自引率
1.10%
发文量
435
审稿时长
4-8 weeks
期刊介绍: BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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