Abstract

Purpose
Lung cancer is frequently observed as a second primary malignancy following gastric cancer, yet the genetic causality between them remains uncertain. This study aims to evaluate the causal relationship between gastric and lung cancers using Mendelian randomization (MR) analysis.
Materials and Methods
Single nucleotide polymorphisms associated with gastric and lung cancers were selected from Genome-Wide Association Study in East Asian and European populations as instrumental variables. The causal effects between gastric and lung cancers were evaluated using univariable and multivariable MR analysis, with the inverse variance weighted (IVW) method serving as the primary criterion. Heterogeneity and sensitivity analyses were performed to ensure the robustness of the findings.
Results
Univariable MR analysis demonstrated that genetic susceptibility to gastric cancer in the European population was significantly associated with an increased risk of lung cancer (IVW: OR:1.285, 95%CI:1.072-1.541, p=6.83E-03), which was consistently validated in the East Asian population (IVW:OR:1.356, 95% CI:1.114-1.651, p=2.40E-03). Multivariable MR analysis further indicated that the significant positive causal relationship between gastric cancer and lung cancer persisted in both populations after adjusting for confounding factors (all p<0.05). Conversely, no significant causal relationship was observed for the risk of developing gastric cancer following the diagnosis of lung cancer diagnosis in either population (p>0.05).
Conclusion
This study confirms that genetic susceptibility to gastric cancer increases the risk of lung cancer. This finding provides a theoretical basis for exploring the underlying biological mechanisms and suggests that enhancing lung cancer screening in patients with gastric cancer may be necessary to improve patient prognosis.

• Keywords: Stomach neoplasms, Lung neoplasms, Risk, Genetic, Mendelian randomization