First, SGMs associated with tobacco smoking were enriched in 14 genes in lung cancer across the three datasets, including TP53, in which most SGMs in the TCGA cohort (51 of 95) were driven by SBS4 (15 SBS4 SGMs expected, FDR = 1.8 × 10−11) (Fig. 3D). Here, TP53 is linked to lung cancer.