The role of senescence indicators in the linkage between high-glycemic food intake and lung cancer: a Mendelian randomization study

High-sugar food intake is linked with elevated lung cancer (LC) risk. Accelerated biological senescence is a risk factor for various diseases. This study probes the role of senescence indicators in the genetic causality between high-sugar food intake and LC risk. Using GWAS data and Mendelian randomization, we found that the intake of sugar added in tea exhibited a significant positive causal association with overall LC risk (OR = 1.310, 95% CI: 1.024-1.675, <i>p</i> = 0.031) and lung squamous cell carcinoma risk (OR = 1.616, 95% CI: 1.089-2.398, <i>p</i> = 0.017). Artificial sweetener intake in cereals was positively linked with small cell lung cancer risk (OR = 4.042, 95% CI: 1.153-14.170, <i>p</i> = 0.029). GrimAge acceleration was significantly correlated with LC risk (<i>p</i> = 0.047), and Hannum age acceleration showed a positive linkage with small cell lung cancer risk (<i>p</i> = 0.002). The intake of sugar added to tea was positively causally linked to both GrimAge (<i>p</i> = 0.045) and Hannum age acceleration (<i>p</i> = 0.025). Mediation analysis indicated that GrimAge acceleration mediated 9.64% of the effect of sugar added to tea on LC risk. In conclusion, high-sugar food intake exhibits a genetic causal linkage with LC risk, partially mediated by biological senescence.