Here, we show that defective MMR (dMMR) interacts with acetaldehyde, in a gene/environment interaction, enhancing dMMR-driven colonic tumour formation in a LS murine model of Msh2 conditional inactivation (Lgr5-CreER; Msh2flox/−, or Msh2-LS) combined with Aldh1b1 inactivation. The gene discussed is MSH2; the disease is colonic neoplasm.