p21WAF1/CIP1 is one of the few genes which shows consistent induction in expression in the rectal mucosa of patients treated with sulindac and deletion of p21WAF1/CIP1 in a mouse model abolished the ability of sulindac to inhibit Apc-initiated tumourigenesis [44], observations which reinforce the hypothesis that p21WAF1/CIP1 acts as a possible downstream effector of COX-2/PGE2/EP4 activity in CRC. This evidence concerns the gene APC and colorectal carcinoma.