Diseases

Genetic testing using blood tests are now available to identify patients with hereditary colon cancer syndromes. Hereditary colon cancer syndromes are caused by specific inherited mutations that are sufficient in themselves to cause colon polyps, colon cancers, and non-colonic cancers. Hereditary colon cancer syndrome can affect multiple members of a family. Approximately 5% of all colon cancers in the US are due to hereditary colon cancer syndromes. Patients who have inherited one of these syndromes have an extremely high risk for developing colon cancer, approaching 90% to 100%. Fortunately, blood tests are now available to test for these hereditary colon cancer syndromes, once a syndrome has been suspected within a family. Familial adenomatous polyposis (FAP) Familial adenomatous polyposis or FAP is a hereditary colon cancer syndrome in which the affected family members develop large numbers (hundreds, sometimes thousands) of colon polyps starting in their teens. Unless the condition is detected and treated early (treatment involves removal of the colon), a family member with the FAP syndrome is almost sure to develop colon cancer. Cancers most commonly begin to appear when patients are in their 40's, but can appear earlier. These patients also are at risk of developing other cancers such as cancers of the thyroid gland, stomach, and the ampulla (the part of the duodenum into which the bile ducts drain). Attenuated familial adenomatous polyposis (AFAP) Attenuated familial adenomatous polyposis or AFAP is a milder version of FAP. Affected patients develop less than 100 colon polyps. Nevertheless, they are at high risk of developing colon cancers at a young age. They are also at risk for stomach and duodenal polyps. Hereditary nonpolyposis colon cancer (HNPCC) Hereditary nonpolyposis colon cancer, or HNPCC, is a hereditary cancer syndrome in which affected family members tend to develop colon cancers, usually in the right colon, in their 30's to 40's. Certain HNPCC patients also are at elevated risk for developing uterine cancer, stomach cancer, ovarian cancer, cancers of the ureters (the tubes that connect the kidneys to the bladder), cancers of the bile ducts (the ducts that drain bile from the liver to the intestines), and cancer of the brain and skin. MYH polyposis syndrome The MYH polyposis syndrome is a recently discovered hereditary colon cancer syndrome. Affected patients typically develop 10-100 polyps during their 40's and are at high risk for developing colon cancer. The MYH syndrome is inherited in an autosomal recessive manner with each parent contributing one copy of the mutant gene. This results in one chance in four that their offspring may inherit both copies of the gene. Most people with the MYH syndrome do not have a multigenerational family history of polyps or cancer of the colon but may have brothers or sisters with it.

Family history: People who have a family history or other risk factors for colon polyps, cancer, or IBD (inflammatory bowel diseases like ulcerative colitis and Crohn's disease) should discuss screening ages and options with their doctor.A genetic syndrome: familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (Lynch syndrome).Those with a positive family history, or diagnosed with a genetic syndrome should begin testing to look for possible early colon cancer at a younger age. This should be discussed with their doctor.Lifestyle factors: Several lifestyle factors increase the risk of colorectal cancer including:

• Obesity
• Alcohol use
• Cigarette smoking
• Sedentary lifestyle (lack of regular physical activity)
• A diet low in fiber and high in fat and red meat

1. Eat a diet high in fruits and vegetables and low in fat and red meat. (This diet also is good for cardio-vascular health.)
2. Take oral calcium supplements and one multivitamin a day that contains 400 micrograms of folic acid. (Calcium supplements also are necessary for maintaining the strength of bones, and folic acid may be good for cardio-vascular health.)
3. Lose excess weight, exercise regularly, and stop smoking cigarettes. (This also is good for cardio-vascular health.)
4. Undergo screening tests for colorectal polyps and cancer. (Note that a new test, Cologuard has been developed and approved by the FDA for home use.)
5. If one has family members with numerous colon polyps, early onset of colon cancers or other cancers such as uterine, stomach, thyroid, and ovarian cancer, talk to your doctor about genetic counseling and testing.

Colonoscopy and flexible sigmoidoscopy (along with digital rectal examination and stool occult blood testing) are the primary and most important tools for both preventing colorectal cancers and detecting early colorectal cancers.Most colorectal cancers arise from colorectal polyps (small growths on the inner lining of the colon and the rectum). Even though colorectal polyps are initially benign, they can grow and change into colorectal cancers over a period of time ranging from five to twenty years. A large study that was conducted in several research centers in the United States showed that patients who had their polyps removed (usually via colonoscopy) had a 90% decrease in colorectal cancer.Early detection and subsequent treatment of abnormal cells or structures (polyps and/or adenomas) can be precancerous or early signs of colon cancer. If these cells and structures are detected and removed by colonoscopic procedures, many colon cancers can effectively be prevented or stopped. The FDA approved Cologuard on August 11, 2014, as the first stool-based (non-invasive) colorectal test that can be used at home to test for blood and abnormal cells in the stool. The test detects hemoglobin (a blood component) and mutations of DNA seen in colorectal cancers. Positive results suggest the patient should undergo a colonoscopy. The safety and effectiveness of this new test was based on a clinical trial involving over 10,000 patients. Cologuard detected 92% of colorectal cancers and 42% of advanced adenomas. The FDA approval was done in conjunction with the approval of Medicare; the test will be covered by Medicare once every three years for patients aged 50 to 85 who are asymptomatic and are at average risk for developing colorectal cancer. The CDC estimates that regular screening tests for colorectal cancer may reduce deaths from this cancer by at least 60%.

Oral supplements of calcium and folic acid, diets high in fruits and vegetables and low in saturated fat and red meat, avoiding obesity, regular exercise, and quitting cigarette smoking are safe measures that probably help to prevent colorectal cancer.Calcium supplements have been shown in animal and human studies to decrease the number of pre-cancerous polyps. Fruits and vegetables contain many chemicals that inactivate cancer-causing chemicals (carcinogens). Obesity, a sedentary life style, cigarette smoking, and high red meat consumption have been linked to an increased risk of colorectal cancer. In a large study of nurses, those who took multivitamins that contained folic acid for decades had less colorectal cancer than women who did not take multivitamins.These measures are considered only "probably" effective because long-term, large-scale, properly designed clinical trials have yet to be performed to establish conclusively that these measures actually prevent colorectal cancer.Doctors are willing to prescribe an agent without conclusive proof of its effectiveness as long as it is safe. In many instances, conclusive proof may be many years away.

NSAIDs (nonsteroidal anti-inflammatory drugs) are widely used in the treatment of arthritis and other inflammatory conditions of the body. Some examples of NSAIDs include aspirin, sulindac (Clinoril), ibuprofen (Advil, Motrin, Nuprin and others), naproxen (Aleve, Naproxyn, Anaprox, Naprelan), and piroxicam (Feldene). How NSAIDs prevent colon cancer and polyps is under investigation. (NSAIDs are potent inhibitors of prostaglandins in the body, and prostaglandins may be important in the formation of polyps.) Why aren't doctors recommending NSAIDs for colorectal cancer prevention? Because NSAIDs can cause stomach ulcers, intestinal bleeding and, sometimes, adverse effects on the liver and kidneys. Even though safer NSAIDs have been developed, doctors generally are reluctant to recommend aspirin or other NSAIDs for preventing colorectal cancer until data on their effectiveness and long-term safety are available. When prescribing an agent for prolonged periods of time to prevent a disease that may or may not occur, the last thing a doctor would want is for that agent to cause adverse side effects in a healthy person.

Anti-oxidants are believed to have anti-cancer effects, but clinical trials using the anti-oxidant vitamins C and A has shown no benefit in preventing colorectal cancer. Many agents or measures that are promising because they have theoretical benefits fall short of expectations when subjected to rigorous clinical trials.

Screening for colorectal cancer is one of the best ways to prevent the disease. Most screening has been done in the recent past by the invasive technique of colonoscopy. Colon cancer screening tests and procedures look for pre-cancerous or cancer cells in people who have no symptoms of disease.Some screening procedures and tests may vary depending on a person's risk factor for colorectal cancer.The new FDA-approved test, Cologuard, is not invasive, less expensive and much easier to accomplish than colonoscopy but it is not a treatment procedure. However, colonoscopy can both screen for precancerous and cancerous conditions and treat many of those (by removing the suspected tissue) during a single invasive procedure.Adults who have no risk factors for colon cancer should begin colon screening at the age of 50.

Genetic counseling followed by genetic testing should be considered for individuals as well as their family members when there are:

• Individuals in the family with early onset of colon cancer, before age 50
• Individuals in the family with numerous colon polyps
• Families in which multiple members have colon cancer
• Families with members with numerous colon polyps
• Families with members having colon cancers at young ages
• Families with members having certain non-colon cancers such as cancers of the uterus, thyroid, ureters, ovaries, small intestine, etc.

Genetic testing without prior counseling is discouraged because of the extensive family education that is involved and the complicated nature of interpreting the test results.

Patients who have hereditary colon cancer syndromes usually have no symptoms and are unaware that they have colon polyps or early colon cancers. They usually will develop colon cancers early in life (often before ages 40-50). Therefore, to prevent colon cancers in patients with hereditary colon cancer syndromes, colon screening must begin early. For example, patients with FAP should have annual flexible sigmoidoscopies starting at age 12, patients with AFAP should have annual colonoscopies starting at age 25, and patients with HNPCC should have colonoscopies beginning at age 25 (or 10 years younger than the earliest colon cancer diagnosed in the family, whichever is earlier). The current screening recommendations for the general population (fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy beginning at ages 40-50) are inadequate for most patients with hereditary colon cancer syndromes. Genetic counseling and testing are important to identify patients and family members with hereditary colon cancer syndromes so that screening with flexible sigmoidoscopies and colonoscopies can begin early and, if necessary, the colon can be removed surgically to prevent colon cancer. Moreover, depending on which hereditary colon cancer syndrome is present, early screening for other types of cancer such as ovarian, uterine, stomach, ureter, and thyroid may be appropriate. The screening role that the new Cologuard test may take is likely to be determined in the near future.