Abstract
BACKGROUND: Liver cancer is a common second primary cancer in gastric cancer patients, but whether a gastric cancer diagnosis contributes to the development of second primary liver cancer remains contentious. This study aims to utilize Mendelian randomization (MR) analysis to investigate the potential causal relationship between gastric cancer and second primary liver cancer from a genetic perspective. METHODS: We extracted single nucleotide polymorphism for gastric cancer and liver cancer in the East Asian population from the Genome-Wide Association Studies database as instrumental variables and employed univariate and multivariate MR analysis to evaluate the causal relationship between gastric cancer and liver cancer. The robustness of the findings was ensured through heterogeneity and sensitivity analyses. RESULTS: Univariate MR analysis revealed that genetic susceptibility to gastric cancer in the East Asian population was significantly associated with an increased risk of liver cancer [Inverse-variance weighted (IVW): OR = 1.252, 95% CI 1.076-1.457, P = 0.004]. Multivariate MR analysis indicated that after adjusting for confounding factors, the significant positive causal relationship between gastric cancer and liver cancer remained robust (all P < 0.05). Furthermore, no causal relationship was observed between liver cancer diagnosis and the development of gastric cancer in the East Asian population (IVW: OR = 1.111, 95% CI 0.936-1.318, P = 0.228). CONCLUSION: Genetic prediction results suggest that gastric cancer survivors might face an increased risk of developing second primary liver cancer, implying the potential value of routine liver cancer screening for gastric cancer survivors.