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Novel metabolomic predictors of incident colorectal cancer in men and women
Journal of the National Cancer Institute ( IF 9.9 ) Pub Date : 2024-10-29 , 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
Journal of the National Cancer Institute ( IF 9.9 ) Pub Date : 2024-10-29 , 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
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.
中文翻译:
男性和女性结直肠癌新发代谢组学预测因子
背景 代谢组学特征可能影响结直肠癌 (CRC) 的发展。很少有研究对 CRC 风险进行诊断前代谢组范围分析。方法 我们在 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)) 中进行了一项嵌套病例对照研究。在 22.9 年中,发生了 684 例 (409 例 NHS,275 例 HPFS) 事件 CRC 病例,并与对照组 1:1 匹配。液相色谱-质谱 (LC-MS) 经质量控制鉴定出 255 种血浆代谢物。使用条件 logistic 回归进行队列特异性和联合代谢物关联分析。代谢物集富集分析 (MSEA) 用于鉴定代谢物类别中的差异丰度。加权相关网络分析 (WGCNA) 提供了协变代谢物模块,这些模块进行了 CRC 关联测试。结果 MSEA 在女性和男性中发现了与 CRC 风险较高的特异性酰基肉碱和与 CRC 风险相关的三酰基甘油。此外,磷脂酰胆碱与男性患 CRC 的风险较高有关。在一项仅限于抽血两年后诊断的 CRC 病例的分析中,肉豆蔻酸 (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 CRC 风险相关。WGCNA 鉴定出男性与 CRC 相关的氨基酸,男性与远端 CRC 相关的脂肪酸酯(肉碱),以及女性与 CRC 呈负相关的三甘油。结论 我们确定了具有不同性别特异性特征的诊断前 CRC 相关代谢物。这些结果提供了对 CRC 发病机制的见解,并对风险预测策略具有意义。
更新日期:2024-10-29
中文翻译:
男性和女性结直肠癌新发代谢组学预测因子
背景 代谢组学特征可能影响结直肠癌 (CRC) 的发展。很少有研究对 CRC 风险进行诊断前代谢组范围分析。方法 我们在 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)) 中进行了一项嵌套病例对照研究。在 22.9 年中,发生了 684 例 (409 例 NHS,275 例 HPFS) 事件 CRC 病例,并与对照组 1:1 匹配。液相色谱-质谱 (LC-MS) 经质量控制鉴定出 255 种血浆代谢物。使用条件 logistic 回归进行队列特异性和联合代谢物关联分析。代谢物集富集分析 (MSEA) 用于鉴定代谢物类别中的差异丰度。加权相关网络分析 (WGCNA) 提供了协变代谢物模块,这些模块进行了 CRC 关联测试。结果 MSEA 在女性和男性中发现了与 CRC 风险较高的特异性酰基肉碱和与 CRC 风险相关的三酰基甘油。此外,磷脂酰胆碱与男性患 CRC 的风险较高有关。在一项仅限于抽血两年后诊断的 CRC 病例的分析中,肉豆蔻酸 (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 CRC 风险相关。WGCNA 鉴定出男性与 CRC 相关的氨基酸,男性与远端 CRC 相关的脂肪酸酯(肉碱),以及女性与 CRC 呈负相关的三甘油。结论 我们确定了具有不同性别特异性特征的诊断前 CRC 相关代谢物。这些结果提供了对 CRC 发病机制的见解,并对风险预测策略具有意义。