Globally, lung cancer is the most prevalent cancer type. However, screening and early detection is challenging. Previous studies have identified metabolites as promising lung cancer biomarkers. This systematic literature review and meta-analysis aimed to identify metabolites associated with lung cancer risk in observational studies. The literature search was performed in PubMed and EMBASE databases, up to 31 December 2019, for observational studies on the association between metabolites and lung cancer risk. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Meta-analyses were performed using either a fixed-effects or random-effects model, depending on study heterogeneity. Fifty-three studies with 297 metabolites were included. Most identified metabolites (252 metabolites) were reported in individual studies. Meta-analyses were conducted on 45 metabolites. Five metabolites (cotinine, creatinine riboside, N-acetylneuraminic acid, proline and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene) and five metabolite groups (total 3-hydroxycotinine, total cotinine, total nicotine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (sum of concentrations of the metabolite and its glucuronides), and total nicotine equivalent (sum of total 3-hydroxycotinine, total cotinine and total nicotine)) were associated with higher lung cancer risk, while three others (folate, methionine and tryptophan) were associated with lower lung cancer risk. Significant heterogeneity was detected across most studies. These significant metabolites should be further evaluated as potential biomarkers for lung cancer.

中文翻译：

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代谢物与肺癌风险之间的关联：系统的文献综述和观察性研究的荟萃分析。

在全球范围内，肺癌是最普遍的癌症类型。但是，筛查和早期发现具有挑战性。先前的研究已将代谢物鉴定为有前途的肺癌生物标志物。这项系统的文献综述和荟萃分析旨在通过观察研究确定与肺癌风险相关的代谢产物。截至2019年12月31日，在PubMed和EMBASE数据库中进行文献检索，以观察代谢物与肺癌风险之间的关系。使用I ²评估异质性统计量和Cochran的Q检验。根据研究的异质性，使用固定效应模型或随机效应模型进行荟萃分析。包括297种代谢物的53项研究被纳入。个别研究报告了大多数鉴定出的代谢产物（252种代谢产物）。对45种代谢产物进行荟萃分析。五个代谢物（可宁碱，肌酐核糖，N-乙酰神经氨酸，脯氨酸和r-1，t-2,3，c-4-四羟基-1,2,3,4-四氢菲）和五个代谢物组（总3-​​羟基烟碱，总可替宁，总烟碱，总4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（代谢产物及其葡糖醛酸化物浓度的总和）和总烟碱当量（总3-羟基烟碱的总和）可替宁和尼古丁总量）与较高的肺癌风险相关，而另外三个（叶酸，蛋氨酸和色氨酸）与降低肺癌风险有关。在大多数研究中均检测到明显的异质性。这些重要的代谢产物应进一步评估为潜在的肺癌标志物。