Managing genetic screening and risk in hereditary colon cancers.
These disorders are hereditary non-polyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, juvenile polyposis syndrome (JPS), and Cowden syndrome.
Fortunately, genetic tests are commercially available for all of these disorders, said Dr. Burt of the University of Utah, Salt Lake City. Patients in whom the mutations are identified require careful medical management to prevent the development of colorectal cancer.
Patients with HNPCC develop only a few adenomas (vs. hundreds or thousands seen in familial adenomatous polyposis), but they carry an 80% lifetime risk for colorectal cancer, which develops at an average age of 44 years. HNPCC also carries an increased risk of other types of cancer, notably endometrial, ovarian, hepatobiliary, gastric, small bowel, ureter, and renal pelvic cancers.
Almost half of all patients with HNPCC can be identified through family history, and this fact has been incorporated in two sets of clinical criteria, known as the Bethesda criteria and the modified Amsterdam criteria. The latter is the simpler of the two, recommending genetic testing if these three criteria are met:
1. At least three relatives diagnosed with HNPCC-related cancers; one must be a first-degree relative of the other two.
2. Colorectal cancer involving at least two generations.
3. At least one relative diagnosed with colorectal cancer before age 50 years.
Those who are found to have the mutation should receive a colonoscopy every 2-3 years starting at age 25, or 10 years younger than the earliest colorectal cancer diagnosis in the family. Although no studies have shown a survival advantage for screening for the related cancers, Dr. Burt said that he routinely offers patients the option of screening for these other tumors as well. Colectomy is typically recommended after diagnosis of colorectal cancer, and some experts recommend prophylactic colectomy, especially if routine surveillance may be problematic.
Patients with Peutz-Jeghers syndrome develop numerous histologically characteristic polyps throughout the gastrointestinal tract. Most patients with the syndrome also have characteristic mucocutaneous pigmentation spots, most commonly on the lips and buccal mucosa but also on other areas, such as the hands, feet, and eyelids.
Patients with Peutz-Jeghers syndrome have a 40% risk of colorectal cancer, a 50% risk of breast cancer, and elevated risks of pancreatic, stomach, small intestinal, esophageal, ovarian, lung, cervical, uterine, and testicular cancers.
Dr. Burt recommended screening colonoscopies every 2-3 years starting in the midteens and annual mammographies beginning in the midtwenties. As in HNPCC, Dr. Burt offers screening for other cancers as well, although evidence for the effectiveness of this practice is lacking.
Treatment of Peutz-Jeghers syndrome involves endoscopic resection of any large polyps.
JPS involves juvenile polyps, mostly in the colon, that are histologically distinct, consisting of dilated cysts filled with mucin and lined by stromal cells. Only one-third of JPS cases appear to be familial. Patients presenting with JPS before the age of 30 often have benign complications from these polyps, but they have a 50% risk of developing colorectal cancer. There also seems to be an elevated risk of other cancers of the upper GI tract, but the exact level of risk remains unknown. While no formal treatment guidelines have been established, Dr. Burt said that a screening colonoscopy every 1-3 years beginning in the late teens seems reasonable.
Cowden syndrome is a rare disorder (occurring in about 1 in 200,000 live births) with characteristic juvenile polyps throughout the GI tract. Patients frequently exhibit trichilemmomas, which often appear as small white bumps on the bridge of the nose. Patients with Cowden syndrome have elevated risk of colon, thyroid, breast, and uterine cancers. Because of the exceptional rarity of this disorder, little evidence exists regarding surveillance or management.
BY ROBERT FINN
San Francisco Bureau
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|Title Annotation:||Genetic Tests Available|
|Publication:||Internal Medicine News|
|Date:||Mar 15, 2004|
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