Causal association between modifiable risk factors and esophageal cancer: A Mendelian randomization study

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.