Can colon cancer run in the family? How age of onset of colorectal cancer tells possible genetic causes? What types of familial colorectal cancer are common? Leading colorectal cancer genetics expert discusses colon cancer. Let's speak about other familial colorectal cancer syndromes. You are a world-renowned expert in colorectal cancer genetics. Dr. Anton Titov, MD. But your life-long interest and achievements in colon cancer treatment and research are driven not only by scientific curiosity, but also by personal history of your entire family. You have just published a book titled "Cancer family: the search for the cause of hereditary colorectal cancer". In that book you tell a dramatic story of several generations of your own family. Many members of your family had colon cancer at a young age. We already spoke about one familial colorectal cancer syndrome - Lynch syndrome. Dr. Anton Titov, MD. But Lynch syndrome is responsible only for about 10 to 25% of cases of familial colorectal cancer. What do we know about other genetic causes of colorectal cancer that might happen across several generations of one family? Dr. C. Richard Boland, MD. Understanding the problem of hereditary colon cancer has taught us a huge amount about the pathogenesis of colorectal cancer. So the very first gene for hereditary colon cancer that was found was the APC gene. Germline mutations in the APC gene cause adenomatous polyposis. What happens is, when you have an inactivation of APC gene, you get excessive uncontrolled proliferation of cells. So you get lots of polyps in large bowel. Eventually the colon polyps will grow. When you have so many polyps - even though one by one any given adenomatous polyp statistically is relatively unlikely to become a colon cancer, but when you have so many, it becomes an overwhelming likelihood that you will get colorectal cancer. So in adenomatous polyposis, colon cancer risk is completely based upon alterations in the regulation of growth of large bowel polyps. In Lynch syndrome, the colon cancer risk is caused by a DNA repair problem. So colon adenomas occur at an ordinary rates, as far as we can tell. But then those adenomas are very likely to become malignant in a short period of time because of the DNA repair problem. There are some other relatively uncommon hereditary colon cancer problems. They have to do with completely different genes altogether. But these other hereditary colon cancer syndromes are quite rare. One of them is Juvenile Polyposis Syndrome. There are several genes that cause it, those are inactivating mutations in genes that are called tumor suppressor gene. So patients lose tumor suppressor function, and cancers can occur. There is another germline mutation in a kinase gene. When that is inactivated, you get Peutz-Jeghers syndrome. Dr. C. Richard Boland, MD. So as we have uncovered the cause of each of these syndromes, we have learned more about colon cancer. And the unexpected finding is that colon cancers is this. We always thought the colon cancer was one uniform disease. but now we know that colon cancer is really a collection of very diverse diseases. This explains why some colon cancers respond to the usual treatments and some don't respond to treatment at all. They are just different diseases.