German researchers have found [significant clinical differences](http://gut.bmjjournals.com/cgi/content/abstract/54/12/1733) in patients with a family history of colorectal cancer and a well-known genetic mutation and those with similar family histories but no mutation.
The team from Munich compared two groups of patients with colorectal cancer, both of which met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC). The first group (25 families) had mutations in either the MLH1 or MSH2 gene as well as high microsatellite instability (MSI) in their tumors.
The second group of 16 families met the Amsterdam criteria for a strong family colorectal cancer history, but did not have MLH1 or MSH2 mutations, and their tumors did not show microsatellite instability.
In addition there were other clinical differences between the two groups:
+ Median age of onset of colorectal cancer was earlier in group 1 than group 2 (41 versus 55)
+ Median age for all tumors was earlier in group 1 (43 versus 56)
+ Group 1 had more additional colorectal tumors found at the same time (synchronous) as well as synchronous tumors outside their colons.
+ Group 1 was more likely to have additional tumors found later (metasynchronous) both in the colon and outside it.
+ Group 2 was more likely to have multiple adenomas, and it appeared that the time it took for adenomas to progress to cancer was longer for them.
+ Tumors in Group 1 were much more likely to be found high in the colon (proximal) versus nearer to the rectum (distal) than those in Group 2. (68% vs. 14%)
The research team concluded:
These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research
The Amsterdam criteria is used to identify families with a particular inherited pattern of colorectal cancer — HNPCC or Lynch Syndrome.
+ One member diagnosed with colorectal cancer before age 50.
+ Two affected generations.
+ Three affected relatives, one of them a first-degree relative of the other two.
+ Familial adenomatous polyposis should be excluded.
+ Tumors should be verified by pathological examination.