Prospective Study of Untargeted Urinary Metabolomics and Risk of Lung Cancer among Never-Smoking Women in Shanghai, China

Abstract

Background: Never-smoking Chinese women have a high rate of lung cancer but the etiology is poorly understood. This study is the first to evaluate the untargeted urinary metabolome and risk of lung cancer among never-smoking women in China. Methods: This nested case-control study included 275 never-smoking lung cancer cases and 289 never-smoking controls from a prospective cohort, the Shanghai Women’s Health Study, comprising 73,363 Chinese women. Metabolic profiling of urinary chemical features was conducted using ultrahigh-performance liquid chromatography - tandem mass spectrometry (UPLC-MS) and nuclear magnetic resonance spectroscopy. Unconditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each log-transformed metabolite and lung cancer risk, after adjusting for potential confounders. Linear regression was used to estimate associations between the most significant metabolites and dietary factors. Results: Initial analyses found that three UPLC-MS detected urinary metabolites were negatively associated with lung cancer risk with a false discovery rate < 10%: pos_2.61_127.0382m/z, neg_2.60_369.0408m/z, and pos_2.61_184.0325n, which were strongly correlated with each other. The most statistically significant metabolite (pos_2.61_127.0382m/z, P = 1.98 x 10-6) was identified as 5-methyl-2-furoic acid and was moderately correlated with self-reported usual dietary intake of soy. Increasing tertiles of the metabolite level were significantly associated with reduced lung cancer risk (OR (95%CI): 1.00, 0.52 (0.34-0.80), 0.46 (0.30-0.70, respectively); P-trend = 1.81 x 10-4). Conclusions: Our findings suggest that soy foods have a protective effect on lung cancer risk in this population of never-smoking women, and are consistent with a previous report from this cohort using questionnaire-based estimates of soy intake. Further studies are needed to replicate and extend the findings.