According to the variable significance results obtained with XGBoost for cancer-adenoma, adenoma–adenoma, and normal-adenoma comparisons in the current study, ADH1C, DEFA5, CPS1, SPP1, DMBT1, VCAN-AS1, and APOB genes can be used as biomarkers for duodenal cancer patients with FAP for cancer-adenoma comparison. Here, SPP1 is linked to cancer.