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. 2025 Jul 14;16(1):1329.
doi: 10.1007/s12672-025-03094-x.

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

Xiaoqing Wang #  1   2   3 , Weiguang Zhang #  1   2   3 , Tianxin Lin #  4 , Renyan Mao  4 , Ye Lin  1   2   3 , Jingchuan Yu  1   2   3 , Limin Ruan  1   2   3 , Jihong Lin  1   2   3 , Lei Gao  1   2   3 , Peipei Zhang  1   2   3 , Zhimin Shen  5   6   7 , Mingqiang Kang  8   9   10   11   12
Affiliations

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

Xiaoqing Wang et al. Discov Oncol. .

Abstract

Background: 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.

Method: 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.

Results: 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.

Conclusions: 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.

Keywords: Esophageal cancer (EC); Mendelian randomization (MR); Modifiable risk factors; Prevention of tumors; Protective factors.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted using data from a previously published database and thus did not necessitate ethical approval. This study was conducted in strict accordance with the relevant guidelines and regulatory standards, upholding the ethical principles for medical research involving human subjects, as detailed in the Declaration of Helsinki. Patient consent for publication: This study was conducted using data from a previously published database and thus cannot obtain patient consent for publication. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Diagrammatic representation of the study design
Fig. 2
Fig. 2
Forest plot of MR analysis between modifiable risk factors and esophageal cancer
See this image and copyright information in PMC

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