Abstract
BackgroundLong-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking.MethodsSerum metabolic profiles and lifestyle information of 464 participants were analyzed. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of smoking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of smoking exposure for ESCC.ResultsEver smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% CI 1.63–6.05), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18–2.13). A total of 5 metabolites were screened as mediators by high-dimensional mediation analysis. In addition, glutamine, histidine, and cholic acid were further proved existing mediation effects according to univariate mediation analysis. And the proportions of mediation of histidine and glutamine were 40.47 and 30.00%, respectively. The mediation effect of cholic acid was 8.98% according to the analysis of smoking index.ConclusionsOur findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by glutamine, histidine and cholic acid.
Highlights
Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear
Multiple logistic regression suggested that ever smoking was associated with a 3.11-fold increase of ESCC risk (OR = 3.11, 95% Confidence interval (CI) 1.63–6.05, P < 0.001), and for each cigarette-years increase in smoking index, ESCC risk increased by 56% (OR = 1.56, 95% CI 1.18–2.13, P = 0.003)
For each cigarette-years increase in smoking index, ESCC risk increased by 56%, and the risk of ever smoking for ESCC is higher (OR = 3.11, 95% CI 1.63–6.05), which was consistent with previous studies [27, 28]
Summary
Long-term smoking exposure will increase the risk of esophageal squamous cell carcinoma (ESCC), whereas the mechanism is still unclear. We conducted a cross-sectional study to explore whether serum metabolites mediate the occurrence of ESCC caused by cigarette smoking. Esophageal squamous cell carcinoma (ESCC) remains the most predominant type of esophageal cancer, and is an important health problem in high-risk areas [1]. Epidemiological studies have found that risk factors for ESCC, including smoking, alcohol drinking, hightemperature foods, diet, and polycyclic aromatic hydrocarbons from a variety of sources [2]. Exposure biomarkers of smoking like nicotine and polycyclic aromatic hydrocarbons, were significantly higher in smokers than non-cigarette users [15, 16]. Cigarette smoking can cause changes in other metabolites, for example, metabolites associated with inflammation and oxidative damage [17]
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