| Summary: | Abstract The role of interleukin (IL)-1 family members/receptors in lung cancer remains uncertain due to the susceptibility of observed associations to confounding. We appraised the association of IL-1 family members/receptors with lung cancer and its subtypes [lung adenocarcinoma (LUAD) and squamous cell lung cancer (LUSC)] using two-sample Mendelian randomization. This study found that no IL-1 family members/receptors were significantly associated with lung cancer and its subtypes risk after correction for multiple testing. However, suggestive total effects of increased risk were noted for genetically predicted IL-1Racp with lung cancer (P = 0.006), IL-1α with LUAD (P = 0.027), and IL-1Racp with LUSC (P = 0.008). Suggestive direct effects were also noted for IL-1β, IL-1Ra, IL-36γ with lung cancer, IL-1α/β, IL-1Ra with LUAD, and IL-1β, IL-18BP with LUSC, after adjusting for genetically predicted effects of other IL-1 family members/receptors. Taken together, our findings suggest that interventions decreasing IL-1Racp might protect against lung cancer, perhaps via IL-1α/β or IL-1Ra.
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