To assess the association between mood swings and pancreatic cancer using two-sample Mendelian randomization (TSMR) and to identify potential mediators between mood swings and pancreatic cancer through multivariable Mendelian randomization (MVMR).

Summary statistics for mood swings were obtained from genome-wide association studies (GWAS). Summary data for pancreatic cancer were derived from a cross-population atlas of 220 human phenotypic genetic associations. Single nucleotide polymorphism (SNP) associated with body mass index (BMI) and several common risk factors for pancreatic cancer, including smoking, alcohol consumption, triglycerides, and total cholesterol, were sourced from the UK Biobank and the IEU database. Causal relationships between mood swings and pancreatic cancer were explored using inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. A series of sensitivity analyses were conducted to evaluate the stability of the results.

Genetically predicted mood swings were positively associated with pancreatic cancer risk, with the IVW method indicating that individuals with genetically determined mood swings had an increased risk of developing pancreatic cancer (OR=2.05, 95%CI: 1.21-3.48). After adjusting for BMI using MVMR, the association between mood swings and pancreatic cancer was attenuated (OR=1.45, 95%CI: 0.94-2.23). Mediation analysis estimated that BMI partially mediated the causal relationship between mood swings and pancreatic cancer risk, with a mediation proportion of 48.2%.

The findings of this study indicate a positive correlation between mood swings and the risk of pancreatic cancer, potentially mediated by effects on BMI.