APC and infection: We observed a significant increase in tumor number in the small intestine of H. pylori-infected Apc+/1638N mice at 12 weeks (Supplementary Figure S1a-c),12 which further increased at 24 weeks post-infection (pi) as shown in previous study.12 Colonic tumors were only observed 24 weeks pi in Apc+/1638N mice.12 These data indicated that the carcinogenesis process was initiated earlier in H. pylori-infected mice (at 12 weeks pi), and thus defined this period as the pre-onset stage of CRC.