Wang Xiaoqing, Zhang Weiguang, Lin Tianxin, Mao Renyan, Lin Ye, Yu Jingchuan, Ruan Limin, Lin Jihong, Gao Lei, Zhang Peipei, Shen Zhimin, Kang Mingqiang
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350000, China.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
Discov Oncol. 2025 Jul 14;16(1):1329. doi: 10.1007/s12672-025-03094-x.
Esophageal cancer (EC), recognized for its aggressive nature, ranks as the sixth leading cause of cancer-associated mortality globally. The incidence of EC has been suggested to link with lifestyle, obesity, and glycemic traits; however, the causality of this association remains uncertain. Consequently, our study aims to elucidate the causal connections between modifiable risk factors and EC.
We adopted single nucleotide polymorphisms (SNPs) as genetic instrumental variables and conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal influence of 14 amendable risk factors on EC, incorporating 740 cases and 372,016 controls.
The data revealed a significant association of coffee intake (OR = 1.003, P = 0.046), smoking (OR = 1.008, P = 0.001), and Body Mass Index (BMI) (OR = 1.001, P = 0.002) with an increased risk of EC. Conversely, type 2 diabetes (OR = 0.999, P = 0.003), education duration (OR = 0.999, P = 0.012), and Low-Density Lipoprotein Cholesterol (LDL-C) (OR = 0.999, P = 0.011) were correlated with a reduced risk of EC.
Our findings suggest that coffee intake, smoking, and BMI potentially contribute as risk factors in the pathogenesis of EC, whereas type 2 diabetes, duration of education, and LDL-C may function as protective elements against the development of this malignancy.
食管癌（EC）因其侵袭性而为人所知，是全球癌症相关死亡的第六大主要原因。有人认为EC的发病率与生活方式、肥胖和血糖特征有关；然而，这种关联的因果关系仍不确定。因此，我们的研究旨在阐明可改变的风险因素与EC之间的因果联系。
我们采用单核苷酸多态性（SNP）作为基因工具变量，并进行了两样本孟德尔随机化（MR）分析，以估计14种可修正风险因素对EC的因果影响，纳入了740例病例和372,016例对照。
数据显示，咖啡摄入量（OR = 1.003，P = 0.046）、吸烟（OR = 1.008，P = 0.001）和体重指数（BMI）（OR = 1.001，P = 0.002）与EC风险增加显著相关。相反，2型糖尿病（OR = 0.999，P = 0.003）、受教育时间（OR = 0.999，P = 0.012）和低密度脂蛋白胆固醇（LDL-C）（OR = 0.999，P = 0.011）与EC风险降低相关。
我们的研究结果表明，咖啡摄入量、吸烟和BMI可能是EC发病机制中的风险因素，而2型糖尿病、受教育时间和LDL-C可能是预防这种恶性肿瘤发生的保护因素。
