# Bidirectional Mendelian Randomisation Analysis of Gastric Cancer and Depression: Evidence for the Causal Effect of Cancer on Depression

## TL;DR

This study shows that gastric cancer causes depression, but depression does not cause gastric cancer, suggesting the need for depression prevention in cancer patients.

## Contribution

The study provides causal evidence using bidirectional Mendelian randomisation that gastric cancer leads to depression.

## Key findings

- Gastric cancer has a causal effect on depression (OR: 1.132, 95% CI: 1.032–1.231).
- Depression does not have a significant causal effect on gastric cancer (OR: 0.834, 95% CI: 0.504–1.380).
- Lactoferrin, lipocalin-2, and matrix metalloproteinase-9 are potential key genes in the shared pathophysiology.

## Abstract

The relationship between gastric cancer and depression is an area of active investigation, and recent studies suggests a bidirectional association. Understanding this relationship is crucial for improving treatment approaches and mental well-being in patients with gastric cancer.

We analysed the correlation between gastric cancer and depression, using data from Genome-Wide Association Studies. Causal links were explored using Mendelian randomisation (MR) and Gene Expression Omnibus.

Forward MR analysis identified 24 single nucleotide polymorphisms (SNPs) meeting the criteria for instrumental variables. The analysis provided evidence of a causal effect of gastric cancer on depression (odds ratio [OR]: 1.132, 95% confidence interval [CI]: 1.032–1.231). The reverse MR analysis, examining the potential causal effect in the opposite direction, identified 15 SNPs; however, no significant causal effect of depression on gastric cancer was detected (OR: 0.834, 95% CI: 0.504–1.380). Cross-pathway analysis identified 23 genes common to both conditions. Protein interaction network analysis of these shared genes revealed that lactoferrin, lipocalin-2 and matrix metalloproteinase-9 are potential key genes in the shared pathophysiology of both diseases.

Our study demonstrates a causal effect of gastric cancer on depression, whereas depression does not exert a causal effect on gastric cancer. These findings provide evidence for targeted depression prevention strategies for patients with gastric cancer.