The potential for activation of pro‐carcinogens by human urothelium observed in this study provides a local mechanism for SNPs previously linked to bladder cancer (CYP1A1, CYP1B1, and ARNT5, 6 and, more recently, POR).16 Despite strong evidence for the association of smoking and occupational BaP exposure with bladder cancer and the support in this study for urothelial activation of PAHs, the smoking‐associated mutational signature seen in lung cancer has not been observed in bladder cancer.7, 42 This may be due to the tissue‐specific nature of extra‐hepatic CYP activity (reviewed in Ref. Here, PPIG is linked to urinary bladder cancer.