Background and Objective: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes.Methods: We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction.Results: Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes (p< 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16–3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09–0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing.Conclusions: The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.
背景与目的：营养代谢组学可能为揭示早期代谢改变及膳食暴露在前列腺癌风险中的作用提供新见解。本研究旨在前瞻性探讨血浆代谢物浓度与前列腺癌风险（包括临床相关肿瘤亚型）之间的关联。 方法：我们采用靶向大规模代谢组学方法，对欧洲癌症与营养前瞻性调查队列中851对匹配的前列腺癌病例-对照血浆样本进行分析。通过多变量条件逻辑回归分析评估代谢物浓度与前列腺癌风险的关联，并使用错误发现率控制多重检验校正。 结果：31种代谢物（主要为食物摄入及微生物代谢衍生物）与总体前列腺癌风险及其临床亚型存在关联（p<0.05），但所有关联均未超过错误发现率阈值。最显著的正向与负向关联分别为：二甲基甘氨酸与晚期前列腺癌风险（比值比=2.13；95%置信区间1.16-3.91，n=157），吲哚-3-乳酸与致死性前列腺癌风险（比值比=0.28；95%置信区间0.09-0.87，n=57），但这些关联经多重检验校正后均未保持统计学显著性。 结论：当前营养代谢组学研究结果表明，除早期代谢失调外，部分食物摄入生物标志物可能与前列腺癌风险（特别是晚期和致死性前列腺癌）存在关联。需要进一步开展独立的大规模研究以验证我们的发现。
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