Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.
JAMA Netw Open. 2019 Sep 4;2(9):e1911970. doi: 10.1001/jamanetworkopen.2019.11970.
Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.
To assess the association between metabolomics and lung cancer risk among never-smoking women.
DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.
Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.
Incident lung cancer.
Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation.
This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.
中国女性在全世界不吸烟女性肺癌患者中肺癌发病率最高，但其病因尚未明确。
评估代谢组学与不吸烟女性肺癌风险之间的关联。
设计、地点和参与者：本巢式病例对照研究纳入了 275 名来自 1996 年 12 月 28 日至 2000 年 5 月 23 日参加前瞻性上海女性健康研究的不吸烟女性肺癌患者和 289 名不吸烟癌症对照参与者。使用经过验证的食物频率问卷收集饮食信息。代谢组学分析于 2015 年 11 月 13 日至 2016 年 1 月 6 日进行。数据分析于 2016 年 1 月 6 日至 2018 年 11 月 29 日进行。
使用预诊断尿样，采用非靶向超高效液相色谱-串联质谱和核磁共振代谢组学图谱对尿液样本进行了特征描述。共测量了 39416 种代谢物。
新发肺癌。
在 564 名女性中，发生肺癌的 275 名参与者（中位[四分位间距]年龄，61.0[52-65]岁）和未发生肺癌的 289 名参与者（中位[四分位间距]年龄，62.0[53-66]岁）在随访期间（中位[四分位间距]随访时间，10.9[9.0-11.7]年）在二手烟暴露、呼吸疾病史和体重指数方面相似。一个峰代谢物，被鉴定为 5-甲基-2-糠酸，与较低的肺癌风险显著相关（比值比，0.57[95%CI，0.46-0.72]；P<0.001；错误发现率=0.039）。此外，该峰与自我报告的膳食大豆摄入量呈弱相关（ρ=0.21；P<0.001）。与第一三分位相比，此代谢物的三分位越高，肺癌风险越低（第二三分位的比值比为 0.52[95%CI，0.34-0.80]；第三三分位的比值比为 0.46[95%CI，0.30-0.70]），并且这种关联在不同的组织学亚型和随访时间上是一致的。此外，代谢途径分析发现与肺癌风险相关的几个系统性生物改变，包括 1 碳代谢、核苷酸代谢、氧化应激和炎症。
这项对中国不吸烟女性的非靶向尿液代谢组学和肺癌的前瞻性研究支持了这样的假设，即基于大豆的代谢物与不吸烟女性较低的肺癌风险相关，并表明与空气污染相关的生物学过程可能与该人群较高的肺癌风险相关。
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