While it is unusual for gastroenterologists to see colorectal tumors in patients under the age of 50, and even more uncommon before the age of 40, it does happen, so patients need to be aware of their risks. Colorectal tumors in young people are often detected either through symptom evaluation or because of a colonoscopy performed for an underlying risk factor, most commonly a family history of colorectal cancer (CRC).
During Colorectal Cancer Awareness Month, the American Gastroenterological Association aims to raise awareness of the importance of family history in colorectal cancer. Genetic testing is an important tool to help gastroenterologists manage their young patients.
When obtaining history or performing an endoscopic evaluation, the key question always is the polyp burden. One needs to make sure the polyps are really adenomas, so as to distinguish hamartomatous (benign malformation of tissue), inflammatory, lymphoid or “sessile serrated” polyps. When adenomas are numerous (more than 10 or 15) in young patients, genetic testing for classic or attenuated familial adenomatous polyposis (FAP and AFAP) and MYH-associated polyposis can be readily performed on blood samples sent to reference laboratories. A positive test will confirm the diagnosis and may influence one’s threshold for considering surgical resection. A positive gene test in an affected patient enables predictive testing in healthy, at-risk relatives; a test-positive relative requires close surveillance, but a test-negative relative can be freed of the need for special surveillance.
When a young person is diagnosed with only one or very few adenomas, we do attempt to more aggressively evaluate family history for a hereditary nonpolyposis CRC (HNPCC) or Lynch syndrome pattern. Testing usually starts with assessment of colon tumor tissue for evidence of so-called “microsatellite instability” or MSI. Benign adenoma tissue can be tested in the same fashion as malignant tumors, though is it commonly less informative. For this reason, if a cancer-affected close relative is identified, an attempt to perform further testing of that person’s tumor may be preferred. Because of the lower yield in adenomas, evaluation of the adenoma is only undertaken when potentially informative cancer tissue from a near relative is unavailable for testing.
A host of considerations enter the decision-making surrounding genetic testing. Does the clinician have suitable genetic counselor support? Clinical testing laboratories can provide excellent molecular diagnostics, but such facilities, even when supported by their own genetic counselors, cannot properly decide whether testing will be beneficial for a particular patient. Real tension exists between the clinical need for careful genetic counseling on the one hand, and the ready availability of very sophisticated genetic testing that can be ordered without any real understanding of its limitations. Indeed, direct-to-consumer marketing of genetic testing and even performance of testing are available. The gastroenterologist uncomfortable with his or her ability to properly counsel the young patient with one or more adenomas can find a wealth of information to enable more informed approaches, or can simply identify and refer to centers with suitable expertise.
To summarize, a genetic workup has three goals: a) to confirm the suspected diagnosis of one of the conditions discussed (HNPCC/LS, AFAP, MAP); b) to potentially change the patient’s clinical management (frequency of colonoscopy, threshold for considering surgical resection, appropriate extracolonic surveillance); c) provide a foundation for predictive genetic testing in other family members, so as to pinpoint those at high risk of similar adenoma involvement, while excluding from further consideration those who are not mutation carriers.
Patrick M. Lynch is a gastroenterologist.