Colorectal cancer and inflammation. Ulcerative colitis and cancer risk. 9
Inflammation increases risk of many cancers. Ulcerative colitis affects risk for colon cancer. How to reduce risk of cancer? Inflammation can increase risk in hereditary colon cancer. Ulcerative colitis increases colon cancer risk. Primary sclerosing cholangitis increases the risks of bile duct cancer, cholangiocellular carcinoma. Chronic pancreatitis raises pancreatic cancer risk. Dr. C. Richard Boland, MD. Gastrointestinal cancers, including colorectal cancer, have many genetic and environmental causes. But two other very important factors play a role in gastrointestinal cancer development. One of them is inflammation. Chronic inflammation in gastrointestinal tract increases frequency of cancer. Colorectal cancer is increased in ulcerative colitis. Primary sclerosing cholangitis increases the risks for the bile duct cancer, cholangiocellular carcinoma. And chronic pancreatitis raises pancreatic cancer risk. How does inflammation increase the risk of gastrointestinal cancers? How does inflammation increase the risk of colorectal cancer? if inflammation happens in the intestines. Chronic inflammation in almost every gut organ increases cancer risk. Inflammation in distal esophagus leads to “Barrett’s esophagus” and esophageal cancer. Chronic gastritis and infection with Helicobacter pylori increases risk for gastric cancer. Even chronically inflamed small intestine – in celiac disease and ulcerative colitis – leads to increased cancer risk. Every time there is chronic inflammation, there’s an increased risk of cancer. What happens is that the inflammatory process does several things. Not just one thing! First, the inflammatory processes itself generates free radicals that damage DNA. So inflammation is mutagenic. The second thing is that the inflammation attracts many inflammatory cells, which then release cytokines and growth factors. Cytokines amplify the immune response. Growth factors also make tumor cells grow too. If you passively put inflammatory cells into an early tumor, cancer could start to grow faster due to these inflammatory cells inside the tumor. Dr. C. Richard Boland, MD. It’s interesting that colon cancers in patients with ulcerative colitis are a bit different. from Lynch syndrome colorectal cancer tumors. They some features of CIMP. [CpG Island Methylator Phenotype] But colon cancers in patients with ulcerative colitis are completely different. They are very aggressive tumors and they have a slightly different genetic signature. Our laboratory and others have found a distinct microRNA signature that is present throughout the colon in people with chronic ulcerative colitis. It might be able to predict, which people with ulcerative colitis are at high risk of colon cancer. It might be nice if you could intervene based on this. If a person with a chronically inflamed colon that needs to be resected eventually, if we know that cancer may develop soon, we should remove the colon sooner rather than later. So I think that little by little we understand more how to use our discoveries in genetics of bowel cancer. But we understand that when there is inflammation, there is mutagenesis. You have growth factors making tumors grow. So it’s really a bad situation in the case of chronic inflammation. Several factors, including free radical formation, compound the risk for cancer in chronic inflammation. Dr. C. Richard Boland, MD. All these factors drive cancer risk and its growth in chronic inflammation. Well, you know. It’s like the the worst of all situations. Inflammation makes free radicals and the mutagenesis causes more mutations. Then you have these other growth factors coming in and fanning the flames of cancer tumor growth. It’s really a very maladaptive situation in the gut when chronic inflammation is present. Dr. Anton Titov, MD.
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