Whereas hypermethylation in the RUNX3 tumor suppressor gene promoter is associated with bladder cancers of smokers [7], our chronic CSE treatment of cultured urothelial cells induced a hypomethylated phenotype at this locus over 4 of 17 CpG sites, with a significant increase in the fraction of the completely unmethylated haplotypes. This evidence concerns the gene RUNX3 and urinary bladder cancer.