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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.