Causal association between hip osteoarthritis and the risk of pancreatic cancer: A bidirectional two-sample Mendelian randomization study

The potential causal relationship between hip osteoarthritis (HOA) and pancreatic cancer (PC) is not well understood. To investigate this, our study utilized a two-sample Mendelian randomization (MR) method to examine a possible causal link between HOA and an increased risk of PC. Genome-wide association study summary data for both HOA and PC were sourced from the Integrative Epidemiology Unit OpenGWAS database (https://gwas.mrcieu.ac.uk/datasets/). The single-nucleotide polymorphisms associated with these conditions at a statistically significant level (P value <5 × 10-8) were identified as instrumental variables for subsequent analysis. We conducted bidirectional two-sample MR analyses employing inverse-variance weighting (IVW), weighted median, MR-Egger regression, and weighted mode methods. The robustness of the findings was assessed through sensitivity testing. The IVW analysis indicated that HOA elevated the risk of PC (odds ratio = 1.788; 95% confidence interval: 1.166-2.742; P = .008). Conversely, in the reverse MR analysis, the IVW analysis provided no evidence that PC increased the risk of HOA (odds ratio = 1.016; 95% confidence interval: 0.973-1.060; P = .475). In addition, the weighted mode, weighted median, and MR-Egger regression methods did not uncover a causal relationship. There was no heterogeneity or horizontal pleiotropy among the instrumental variables. The "leave-one-out" analysis revealed that no single-nucleotide polymorphism significantly influenced the overall results. Genetically predicted HOA is significantly associated with an increased risk of PC. However, we found no evidence that PC leads to an increased risk of HOA.