With regard to the clinical relevance of COX-2 in the pathogenesis of CRC, Veettil and colleagues published a systematic review in 2019 concluding that the benefit of CRC chemoprevention with COX-2-inhibitor celecoxib outweighed the risk of cardiovascular side effects after reviewing three randomized controlled trials and three post-trial studies which compared the incidence of recurrence of colorectal adenomas in patients given celecoxib at varying doses or placebo [193]. This evidence concerns the gene PTGS2 and colorectal adenoma.