Connecting atrial fibrillation to digestive neoplasms: exploring mediation via ischemic stroke and heart failure in Mendelian randomization studies

TL;DR

This study finds that genetic predisposition to atrial fibrillation increases risk of certain digestive cancers, partly through heart failure and stroke.

Contribution

Novel use of Mendelian randomization to identify ischemic stroke and heart failure as mediating pathways between atrial fibrillation and digestive neoplasms.

Findings

Genetic AF predisposition causally links to colon, esophageal, and small intestine cancers.

Ischemic stroke mediates AF's effect on colon cancer risk.

Heart failure partially mediates AF's effect on esophageal and small intestine cancer risk.

Abstract

Notwithstanding the acknowledged interplay between atrial fibrillation (AF) and the emergence of digestive system neoplasms, the intricacies of this relationship remain ambiguous. By capitalizing univariable Mendelian Randomization (MR) complemented by a mediated MR tactic, our pursuit was to elucidate the causative roles of AF in precipitating digestive system malignancies and potential intermediary pathways.

This research endeavor seeks to scrutinize the causal clinical implications of whether genetic predispositions to AF correlate with an increased risk of digestive system malignancies, employing MR analytical techniques. Utilizing a dataset amalgamated from six studies related to AF, encompassing over 1,000,000 subjects, we performed univariable MR assessments, employing the random-effects inverse-variance weighted (IVW) methodology as our principal analytical paradigm. Subsequently, a mediated MR framework was employed to probe the potential mediating influence of AF on the nexus between hypertension (HT), heart failure (HF), ischemic stroke (IS), coronary artery disease (CAD), and digestive system neoplasms.

The univariable MR evaluation unveiled a notable causal nexus between the genetic inclination toward AF and the genetic susceptibility to colon, esophageal, and small intestine malignancies. The mediated MR scrutiny ascertained that the genetic inclination for AF amplifies the risk profile for colon cancer via IS pathways and partially explains the susceptibility to esophageal and small intestine tumors through the HF pathway.

Our investigative endeavor has highlighted a definitive causative association between genetic inclination to AF and specific digestive system neoplasms, spotlighting IS and HF as instrumental mediators. Such revelations furnish pivotal perspectives on the complex genetic interconnections between cardiovascular anomalies and certain digestive tract tumors, emphasizing prospective therapeutic and diagnostic worthy of pursuit.

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