Polymorphisms in PG/COX Pathway and Colorectal Polyps

Cancer Prevention Program

Polymorphisms in PG/COX Pathway and Colorectal Polyps

PI: Neli Ulrich PhD

Aspirin and other anti-inflammatory drugs called NSAIDs reduce the recurrence of colorectal polyps among patients with a form of familial colon cancer called familial adenomatous polyposis (FAP). These drugs are also associated with a lower risk of polyp development and colorectal cancer in people without this specific cancer syndrome. Primary targets for these drugs are the cyclooxygenase (COX1 and COX2) enzymes in the prostaglandin (PG) pathway.

The goal of this study is to evaluate the association between common genetic changes (polymorphisms) in enzymes, growth factors, and receptors linked to prostaglandin synthesis or COX activity and the risk of precancerous colon polyps. Currently, very few polymorphisms in this pathway have been reported. Thus, we aim to identify new genetic polymorphisms in this pathway and to investigate the potential impact of these polymorphisms on enzyme function. We intend to screen selected enzymes in the prostaglandin pathway for new polymorphisms by several techniques.

After searching for polymorphisms in our selected genes, we propose to investigate 5 to 10 genetic polymorphisms in COX1,COX2, and other enzymes in the prostaglandin pathway, or growth factors and receptors related to it, and their association with colorectal polyps through a case-control study. We will 1) investigate the main effects of the genetic polymorphisms, and 2) investigate whether these polymorphisms modify the association between environmental factors (in particular aspirin and NSAID use) and colorectal polyps. Finally, we plan to develop a mathematic model to describe how genetic variability affects the larger metabolic pathway.