Analysis of changes in pathways in colonocytes revealed that the pathways associated with cell cycle checkpoints were downregulated across all three polyp subtypes, while the p53 pathway and apoptosis were uniquely downregulated in colonocytes of PJS polyps, which suggested that STK11/LKB1 mutation made colonocytes prone to DNA damage and malignancy in PJS polyps, while p53‐targeted drugs may be used to delay polyp progression in PJS patients. This evidence concerns the gene TP53 and Peutz-Jeghers syndrome.