测量诊断前血液代谢物可能有助于识别前列腺癌的新危险因素。使用来自欧洲癌症与营养前瞻性调查 (EPIC) 研究的 4387 个匹配病例对照对的数据，我们研究了 148 种单独代谢物和三种先前定义的代谢物模式与前列腺癌风险的关联。通过液相色谱-质谱法测量代谢物。使用多变量调整条件逻辑回归来估计总体前列腺癌以及晚期、高级别、侵袭性前列腺癌的对数代谢物浓度和代谢物模式 (OR1SD) 每标准差增加的优势比。我们使用 Benjamini-Hochberg 方法纠正了多次测试。总体而言，特定代谢物或代谢物模式与通过多重测试阈值的总体、侵袭性或高级别前列腺癌之间没有关联（padj <0.05）。六种磷脂酰胆碱 (PC) 与采血后 10 年内诊断出的晚期前列腺癌呈负相关。代谢物模式1（64种PC和三种羟基鞘磷脂）和2（两种酰基肉碱、谷氨酸、鸟氨酸和牛磺酸）也与晚期前列腺癌呈负相关；当按随访时间分层时，在招募后 10 年内或之内观察到这些相关性（OR1SD 0.80，95% CI 分别为 0.66-0.96 和 0.76，0.59-0.97），但在更长的随访后更弱（0.95） ，0.82-1.10 和 0.85，0.67-1.06）。模式 3（8 个溶血 PC）与前列腺癌死亡相关（0.82，0.68-0.98）。我们的结果表明，在检测到晚期疾病之前十年，血浆代谢物谱会因前列腺癌的存在而发生变化。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.