Colon Cancer & Heredity

Excluding skin malignancies, colorectal cancer is the third most common cancer diagnosed among American men and women. (The leading cancers for men are lung and prostate cancers; for women, the leading cancers are lung and breast cancers.) About 130,000 new cases of colorectal cancer are diagnosed each year. Six percent of all Americans, 1 out of every 17, will develop colorectal cancer.

Though most cases occur sporadically, it is estimated that 5 to 10 percent of all colorectal cancers are explained by a specific genetic susceptibility. A person who is diagnosed with colorectal cancer and who has a family history of the disease is more likely to have inherited a cancer gene than a person with no family history of colorectal cancer.

HNPCC is a syndrome that accounts for approximately 5 percent of all colorectal cancer diagnoses. The syndrome is caused by mutations in specific genes, which are described below. Families with HNPCC typically have:

• Three or more closely related family members diagnosed with colorectal cancer
• Affected family members in two or more generations
• At least one person with colorectal cancer diagnosed before the age of 50

The average age of colorectal cancer onset in families with HNPCC mutations is 45 years. Though colorectal cancer is the most common malignancy reported in families with HNPCC, the syndrome is also associated with an increased risk for cancers of the uterus, ovaries, stomach, small intestine, biliary system, pancreas, and urinary tract.

There are families with strong histories of colorectal cancer but in whom HNPCC mutations have not been detected. These families may carry mutations in genes yet to be identified, or there may not be a mutation at all, the cancer history possibly being explained by ill chance.

There are other rare forms of hereditary colon cancer. One of these is called familial adenomatous polyposis. In this condition, children develop hundreds or thousands of polyps in the colon at a very early age. These children will almost always go on to develop colon cancer by age 40. There are two other, milder hereditary colorectal syndromes, known as attenuated familial adenomatous polyposis (AFAP) and MYH-associated polyposis. Less is known about these two recently discovered syndromes.

For more information about these other hereditary colon cancer syndromes, see About Familial Adenomatous Polyposis.

You should think about the following benefits and risks before you undergo genetic testing.

Benefits

• Genetic test results may allow for a more accurate assessment of a person's cancer risk. If the results are positive, doctors can screen earlier as described above to look for colorectal cancer and other HNPCC-associated cancers. If the results are negative, individuals may not have to screen as aggressively.
• If a mutation is identified, genetic testing and/or early cancer screening can be offered to other at-risk family members.
• There is no physical risk involved in genetic testing, other than that of a routine blood draw.

Risks

• Genetic testing can be emotionally difficult regardless of the results.
• If a mutation is found, relatives who have not had genetic testing may make assumptions about their own genetic status.
• The costs associated with cancer screening and prevention for people with mutations may or may not be covered by their health insurance provider.
• There is also the possibility of employer discrimination or insurance provider discrimination based on genetic test results. Insurers may seek higher premiums or cancel/deny policies for individuals with pre-existing genetic conditions. In New York State, a person's genetic test results cannot be given to anyone else without the written permission of the person who is tested. Genetic testing at Memorial Hospital is generally offered within the context of a research study. Test results are therefore stored in research files that are kept separate from regular medical records. We have obtained certificates of confidentiality from the National Institutes of Health to protect the research information contained in these files. Should a person receive genetic counseling for cancer risk based solely on family history however, that information will become part of their medical record. Should a person choose to share their genetic test results with another healthcare professional, that information may also become part of their medical record. At present, we are not aware of any instances of discrimination against families who have received genetic testing as part of research studies at Memorial Hospital.

Even if you don't want to take part in a study and/or receive genetic testing, you should talk to your doctor about your family history of colorectal cancer. If any one of your close relatives has had colorectal cancer, you have an increased chance of developing colorectal cancer as well. Speak with your doctor about your family history of colorectal cancer and discuss appropriate screening recommendations to lower your risk of developing this disease. Even if you don't wish to have genetic testing, you are welcome to make an appointment at the Clinical Genetics Service to discuss your family history and learn about cancer screening recommendations.

Your family history can serve as a guide to help you determine your risk for colon cancer. Your gastroenterologist, internist, or cancer geneticist can provide you with guidelines based on your family history. For example, in many families we will recommend that colonoscopy screening begin ten years before the age of onset of cancer for the youngest affected person in your family. There are also research studies involving diet and "chemoprevention" measures that you may consider.

At Memorial Sloan-Kettering, colonoscopy is considered the "gold standard" for colon cancer screening. During a colonoscopy, the doctor passes a thin flexible tube through the anus to look inside the colon. In other settings, doctors may perform sigmoidoscopy, which visualizes only the last third of the colon. Newer tests such as "virtual colonoscopy" are being developed that allow imaging of the colon.

If someone else in your family has already tested positive for a gene mutation, you may be tested for the specific mutation found in their sample. If you have tested negative for a mutation that's known to run in your family, no further testing is needed.

For more information on cancer syndromes related to the APC and MYH genes, see About Familial Adenomatous Polyposis.