Relationship between creatine kinase and gastric cancer: A two-sample Mendelian randomization study

Observational studies have suggested associations between circulating creatine kinase (CK) levels and gastric cancer (GC), yet causality remains uncertain. To evaluate whether genetically predicted CK levels are causally related to GC risk, and vice versa, using a 2-sample Mendelian randomization (MR) design. A 2-sample MR design was employed, incorporating statistical methods such as inverse-variance weighting (IVW), Weighted Median, and MR-Egger regression. Candidate single-nucleotide polymorphisms associated with CK and GC were identified from genome-wide association studies datasets. Heterogeneity was assessed using Cochrane Q test, and horizontal pleiotropy was evaluated through MR-Egger regression and leave-one-out analyses. The primary analysis using IVW showed no significant causal relationship between CK and GC (P = .09, 95% CI = -0.36 to 0.03, OR = 0.84). Similarly, MR-Egger regression (P = .29, 95% CI = -0.83 to 0.24, OR = 0.74) and other sensitivity analyses (weighted median, simple mode, weighted mode) did not support a causal link (all P > .05). When GC was used as the exposure, no significant causal effect was observed on CK levels (IVW: P = .80, 95% CI = -0.03 to 0.02, OR = 1.00; MR-Egger: P = .46, 95% CI = -0.83 to 0.24, OR = 0.74). These findings were consistent across all MR methods and sensitivity analyses. Our study did not identify a genetic causal relationship between CK and GC. Further population-based and experimental studies are needed to elucidate the complex relationship between CK and GC.