Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, China.
Front Public Health. 2023 Mar 28;11:1022367. doi: 10.3389/fpubh.2023.1022367. eCollection 2023.
Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role.
Using summary statistics from genome-wide association studies (GWASs) based on European ancestry individuals of several years in education (EduYears, primary analysis, = 293,723), college completion (College, secondary analysis, = 95,427), EC ( = 420,531), BE ( = 361,194), and GERD ( = 420,531), genetic associations between two education phenotypes and EC, BE, and GERD were tested by two-sample MR analyses. Then, two-step MR mediation analyses were used to assess the proportion of the aforementioned association that might be mediated by body mass index (BMI), major depressive disorder (MDD), smoking, drinking, carbohydrates, fat, and protein intake.
Genetically predicted EduYears was negatively associated with the risk of EC, BE, and GERD {odds ratio (OR), 0.64 [95% confidence interval (CI) 0.44-0.94], 0.86 (95% CI, 0.75-0.99), and 0.62 (95%CI, 0.58-0.67)}. EduYears was negatively associated with BMI, MDD, and smoking (range of OR: 0.76-0.84). There were positive associations between BMI, smoking with EC, BE, and GERD, as well as between MDD with GERD (range of OR: 1.08-1.50). For individual mediating effect, BMI and smoking mediated 15.75 and 14.15% of the EduYears-EC association and 15.46 and 16.85% of the EduYears-BE association. BMI, MDD, and smoking mediated 5.23, 4.98, and 4.49% of the EduYears-GERD association. For combined mediation, the aforementioned mediators explained 26.62, 28.38, and 11.48% of the effect of EduYears on EC, BE, and GERD. The mediating effects of drinking and dietary composition were not significant in the effect of education on EC, BE, and GERD.
Our study supports that genetically predicted higher educational attainment has a protective effect on EC, BE, and GERD, and is partly mediated by reducing adiposity, smoking, and depression.
观察性研究报告称，教育程度与食管癌（EC）及其癌前病变的风险有关。然而，因果关系仍存在争议。我们旨在应用孟德尔随机化（MR）设计来确定遗传预测的教育程度与 EC、巴雷特食管（BE）和胃食管反流病（GERD）之间的因果关系，并探讨可改变的风险因素是否起中介作用。
使用基于欧洲血统个体多年教育（EduYears，主要分析，= 293723）、大学毕业（College，次要分析，= 95427）、EC（= 420531）、BE（= 361194）和 GERD（= 420531）的全基因组关联研究（GWAS）汇总统计数据，通过两样本 MR 分析检验两种教育表型与 EC、BE 和 GERD 之间的遗传关联。然后，使用两步 MR 中介分析评估上述关联中可能由体重指数（BMI）、重度抑郁症（MDD）、吸烟、饮酒、碳水化合物、脂肪和蛋白质摄入介导的比例。
遗传预测的 EduYears 与 EC、BE 和 GERD 的风险呈负相关（比值比[OR]，0.64 [95%置信区间[CI]，0.44-0.94]、0.86（95%CI，0.75-0.99）和 0.62（95%CI，0.58-0.67））。EduYears 与 BMI、MDD 和吸烟呈负相关（OR 范围：0.76-0.84）。BMI、吸烟与 EC、BE 和 GERD 呈正相关，MDD 与 GERD 呈正相关（OR 范围：1.08-1.50）。对于个体中介效应，BMI 和吸烟分别介导了 EduYears-EC 关联的 15.75%和 14.15%，以及 EduYears-BE 关联的 15.46%和 16.85%。BMI、MDD 和吸烟分别介导了 EduYears-GERD 关联的 5.23%、4.98%和 4.49%。对于综合中介作用，上述中介因素解释了 EduYears 对 EC、BE 和 GERD 影响的 26.62%、28.38%和 11.48%。饮酒和饮食成分的中介作用在教育对 EC、BE 和 GERD 的影响中并不显著。
我们的研究支持遗传预测的较高教育程度对 EC、BE 和 GERD 具有保护作用，部分原因是通过降低肥胖、吸烟和抑郁来实现。
