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

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.