What are typical symptoms of colorectal cancer? Symptoms of early stage colon cancer and late stage colorectal cancer symptoms can be different. How do people discover they have Lynch syndrome? Dr. C. Richard Boland, MD. Big, big problem with colon cancer is that it does not cause symptoms until it's quite late in its course. A person who has a distal colon cancer, for example, in the sigmoid colon might experience a bowel obstruction. But other people with colon cancer might just slowly bleed and have anemia. Even more often an early stage colon cancer has no symptoms at all. So people who have colon cancer don't know they have it unless colon cancer is advanced in stage. In cases of hereditary forms of colon cancer people might be on the alert that they could be in a familiar colorectal cancer situation for 3 reasons: if they had an early onset colon cancer, if they had multiple colon cancers in their lifetime. if there is a positive family history of colon cancer. That would be three major ways of knowing about hereditary colon cancer: positive family history, early onset, multiple tumors in one person. Is there a difference in the symptoms and presentation between the colon cancers located in the more proximal parts of colon versus the more distal colon cancers? That's a good point! Two thirds of Lynch syndrome colon cancers are in the proximal colon. The proximal colon is bigger in diameter. It is very unlikely to become obstructed. Dr. C. Richard Boland, MD. But proximal colon is likely to bleed. So oftentimes a person with a cancer in the cecum or ascending colon or transverse colon will have bleeding. These patients will present with anemia. 30% of tumors in the proximal colon. It is not only hereditary colon cancers, but also non-hereditary tumors too. they have phenotype called "microsatellite instability". Microsatellite instability generates a number of immunogenic peptides, which then brings a lot of inflammatory cells into the tumor. So patients get symptoms of inflammation: pain or a lot of weight loss, probably caused by the cytokines that are made by all that immune activity. Because there is a huge biological battle between the tumor and the infiltrating lymphocytes. But, as you mentioned previously, having abdominal pain is quite late symptom of colorectal cancer Yes, that's true. And our goal is to find ways to diagnose colon cancer before there's pain as a symptom. So that's where the surveillance and screening of precancerous and early cancerous lesions is very important. Yes, for most people in North America and in Europe, most - 95% - of the colorectal cancers are sporadic. So we sometimes find that a person is a "polyp former". They get polyps that might even occur in a family. Polyp formation might be caused by shared family dietary or other environmental exposures much more so than by genes. So if we find someone at a high risk for colon cancer due to increased polyp formation, Then we might start a colonoscopy regimen. But even a very aggressive colonoscopy regimen would be doing another colonoscopy every five years. Because of the known slow progression from the adenoma to carcinoma. Dr. C. Richard Boland, MD. So patients don't really have to do colonoscopies more than every five years. And in some instances the risks of colon cancer are only moderate, So colonoscopy every 10 years would be good enough. But in a case of Lynch syndrome there is a very accelerated adenoma to carcinoma progression. So colonoscopies have to be done every year. But when we do the colonoscopies every year, it dramatically alters the natural history of Lynch syndrome and prevents people from getting cancers to begin with. So that is a wonderful result. We are able to prevent colon cancer, and not just find the cancer early and do the surgical operation. We can remove polyps during screening colonoscopy and prevent colon cancer. So we have people who know that they have Lynch syndrome, we found the germline mutation, but they get their colonoscopies regularly, and they get to be in their 60s and 70s, and they have never had colon cancer. Dr. Anton Titov, MD.