Existing air pollution metabolomics studies showed inconsistent results, often limited by small sample size and individual air pollutants effects. We conducted a metabolome-wide association study among 1096 women (68.2 ± 5.7 years) who provided blood samples (1998–2001) within the Cancer Prevention Study-II Nutrition Cohort. Annual average individual exposures to particulate matter, nitrogen dioxide, ozone, sulfur dioxide, and carbon monoxide in the year of blood draw were used. Metabolomics profiling was conducted on serum samples by Metabolon. We evaluated the individual air pollutants effects using multiple linear regression and the mixture effect using quantile g-computation, adjusting for confounders and false discovery rate (FDR). Ninety-five metabolites were significantly associated with at least one air pollutant or mixture (FDR < 0.05). These metabolites were enriched in pathways related to oxidative stress, systemic inflammation, energy metabolism, signals transduction, nucleic acid damage and repair, and xenobiotics. Sixty metabolites were confirmed with level 1 or 2 evidence, among which 21 have been previously linked to air pollution exposure, including taurine, creatinine, and sebacate. Overall, our results replicate prior findings in a large sample and provide novel insights into biological responses to long-term air pollution exposure using mixture analysis.

中文翻译：

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暴露于环境空气污染的代谢组学特征：癌症预防研究 II 营养队列中的大规模全代谢组关联研究


现有的空气污染代谢组学研究显示结果不一致，通常受到样本量小和个体空气污染物影响的限制。我们在癌症预防研究 II 营养队列中提供的 1096 名女性 （68.2 ± 5.7 岁） 中进行了全代谢组关联研究 （1998-2001）。使用抽血当年个体对颗粒物、二氧化氮、臭氧、二氧化硫和一氧化碳的年平均暴露量。通过 Metabolon 对血清样品进行代谢组学分析。我们使用多元线性回归评估了单个空气污染物效应，使用分位数 g 计算评估了混合效应，并调整了混杂因素和错误发现率 （FDR）。95 种代谢物与至少一种空气污染物或混合物显著相关 （FDR < 0.05）。这些代谢物富含与氧化应激、全身炎症、能量代谢、信号转导、核酸损伤和修复以及外源性生物相关的途径。60 种代谢物通过 1 级或 2 级证据得到证实，其中 21 种先前与空气污染暴露有关，包括牛磺酸、肌酐和癸二酸酯。总体而言，我们的结果在大样本中复制了先前的发现，并使用混合物分析为生物对长期空气污染暴露的反应提供了新的见解。