Among the known facts about colon cancer are these: Usually it begins as a small polyp in the lining of the intestines, and, compared to other cancers, it progresses slowly over several years. Because this cancer occurs in the digestive tract, scientists have often considered important links to diet. Now new evidence verifies a connection to dietary fats, such as those found in processed meats, butter, beef and pork fat, shortening, and margarine. Dr. Raymond DuBois, of Arizona State University, has identified a molecule, called peroxisome proliferator-activated receptor delta (PPAR delta), which, when deleted in mice with colon cancer, stopped the progression of tumor growth.
Diet and Cancer
Known risks for colorectal cancers — tumors affecting the colon and the rectum are commonly grouped together as they affect the digestive tract — include family history, inflammatory bowel disease, smoking, and type 2 diabetes. Foods high in saturated fats may also increase risk and so general advice to help you avoid colorectal cancer is to focus on your diet. Recent, large studies, for instance, suggest that fiber, especially from whole grains, may lower colorectal cancer risk. Doctors also recommend you limit your intake of red and processed meats, eat more vegetables and fruits, watch your weight (especially watch for gains around the midsection), avoid excessive alcohol (ho-hum) and get recommended levels of calcium and vitamin D, which may work together to prevent these cancers.
Unusually, studies have shown the use of nonsteroidal anti-inflammatory drugs (NSAIDs) — such as aspirin, Celebrex, and Motrin — may reduce the risk of developing colorectal cancer by 40 to 50 percent. NSAIDs target an enzyme called cyclooxygenase 2 (or COX-2). COX-2 helps to carry out steps to produce the pro-inflammatory molecule prostaglandin E2 (PGE2), which is found at high levels in colorectal tumors.
Pursuing links between inflammation and colon cancer, DuBois' research team sought to uncover the key molecular steps regulating the COX-2/PGE2 pathway. The peroxisome is considered to be the cell’s special garbage pail for dietary fat and also the place where peroxisome proliferator-activated receptors or PPARs are found. PPARs are central players in regulating the breakdown and storage of fats within a cell. The DuBois team decided to investigate the role of the PPAR delta, which is a gene that instructs the cell to make PPARs, to see what its effect on chronic inflammation and colorectal cancer progression might be.
In a mouse model of colon cancer, the team "knocked out" the PPAR delta and found that the mice showed no signs of chronic inflammation. Furthermore, when looking at the immune response, they found none of the usual immune cells associated with inflammation. They also measured the levels of COX-2 and found that loss of PPAR had no effect on COX-2 expression.
"This provides us with an important new clue in designing and developing a therapeutic arsenal to stop the initiation and progression of colon cancer," DuBois said in a press release. He feels confident in this new finding in part because when elevated levels of PPAR delta and COX-2 are found in tumor tissues that usually means a poor prognosis for the patient. He and his team hope to develop new drugs to block PPAR delta as a way to treat both inflammatory bowel disease and colorectal cancer.
Source: DuBois R, Wang D, Fu L, et al. Proceedings of the National Academy of Sciences. 2014.