Novel metabolomic predictors of incident colorectal cancer in men and women.

IF 9.9 1区 医学 Q1 ONCOLOGY JNCI Journal of the National Cancer Institute Pub Date : 2024-10-28 DOI:10.1093/jnci/djae270
Jonathan M Downie, Amit D Joshi, Connor M Geraghty, Brendan J Guercio, Oana A Zeleznik, Mingyang Song, Alaina M Bever, David A Drew, Fred K Tabung, Xuehong Zhang, Lina Jin, A Heather Eliassen, Walter C Willett, Kana Wu, Peter Kraft, Rulla Tamimi, Clary Clish, Charles S Fuchs, Edward Giovannucci, Jeffrey A Meyerhardt, Andrew T Chan
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Abstract

Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association.

Results: MSEA identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women.

Conclusions: We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.

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男性和女性结直肠癌发病的新代谢组学预测因素。
背景:代谢组谱可能影响结直肠癌(CRC)的发展。很少有研究对诊断前代谢组与 CRC 风险进行整体分析:我们对 1989 年至 1995 年间提供血液的女性(护士健康研究(NHS))和男性(卫生专业人员随访研究(HPFS))进行了一项嵌套病例对照研究。在 22.9 年的时间里,共发现了 684 例(409 例 NHS,275 例 HPFS)儿童癌症病例,并与对照组进行了 1:1 的配对。经过质量控制后,液相色谱-质谱法(LC-MS)鉴定出 255 种血浆代谢物。采用条件逻辑回归法进行了同组特异性和合并代谢物关联分析。代谢物集富集分析(MSEA)用于确定代谢物类别的丰度差异。加权相关网络分析(WGCNA)提供了共变代谢物模块,并对其与 CRC 的相关性进行了检测:结果:在女性和男性中,MSEA 发现了与较高的 CRC 风险相关的特定酰基肉碱,以及与较低的 CRC 风险相关的三酰甘油。此外,在男性中,磷脂酰胆碱与较高的 CRC 风险相关。在一项仅限于抽血两年后确诊的 CRC 病例的分析中,肉豆蔻油酸(OR = 1.37;95%CI = 1.15-1.62;FDR = 0.072)和 C60:12 三酰甘油(OR = 0.75;95%CI = 0.64-0.88;FDR = 0.072)与女性的 CRC 风险有关。WGCNA 发现氨基酸与男性的 CRC 相关,脂肪酸酯(肉毒碱)与男性的远端 CRC 相关,三酰甘油与女性的 CRC 成反比:结论:我们发现了诊断前与 CRC 相关的代谢物,它们具有不同的性别特异性特征。结论:我们发现了诊断前与 CRC 相关的代谢物,这些代谢物具有不同的性别特异性特征。这些结果有助于深入了解 CRC 的发病机理,并对风险预测策略产生影响。
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来源期刊
CiteScore
17.00
自引率
2.90%
发文量
203
审稿时长
4-8 weeks
期刊介绍: The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.
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