Welcome back. Thanks for joining me on this discussion of colon cancer under the section of large intestines.
What are the causes of colon cancer? I’ll give you a second to think about this. Here are some
very important colon cancer risk factors: low fiber, high fat diet, we call this the Western diet;
there are important hereditary syndromes to be aware of; gene mutations from a polyp all the way
to cancer in a predictable fashion; and inflammatory bowel disease including ulcerative colitis and
Crohn’s disease. Ulcerative colitis and Crohn’s disease will be covered in your medicine lectures.
Let’s start with one of the very important syndromes, hereditary nonpolyposis colorectal cancer, HNPCC.
HNPCC or typically described as either Lynch syndrome 1 or Lynch syndrome 2. Lynch syndrome 1
is an autosomal dominant phenotype and classically associated with the DNA mismatch repair gene,
MLH or MSH. On your examination, when presented with a particular DNA mismatch repair gene,
look for this as the answers. In Lynch syndrome 2, it’s similar to an autosomal dominant Lynch
syndrome 1 except that now you have extracolonic cancers particularly endometrial or ovarian. Peutz-Jeghers,
another important syndrome, autosomal dominant phenotype. These are classically associated with
hamartomas which are benign in the GI tract, also associated with mucocutaneous
pigmentation. However, although the hamartomas are benign, there is an increased risk of
associated GI cancers, not derivatives of the hamartomas. How about familial adenomatous polyposis?
These are multiple colon polyps and usually in the thousands. There is APC or adenomatous
polyposis coli gene which is a tumor suppressing gene mutation. As a reminder in general, when
a tumor suppressing gene mutation occurs, there’s no tumor suppression. Just like many of the other
polyposis syndromes, this is also autosomal dominant in nature. Typically, you’ll find hundreds
or thousands of polyps and there’s almost 100% guaranteed risk of colon cancer due to the pure
volume of polyps. Shortly, we’ll discuss the very predictable line of polyp to colon cancer and why
often FAP patients will require surgery. Gardner syndrome, another high-yield syndrome,
again associated with colon polyposis. This is considered a subset of familial adenomatous polyposis that we
just talked about. The difference here is that it’s a multiple polyposis syndrome
that’s associated with extracolonic manifestations such as desmoid tumors, sebaceous cysts,
lipomas, and osteomas. When you’re presented with a clinical scenario that shows extracolonic
manifestations as well as polyposis, remember Gardner syndrome.