Genetic Testing for Colon Cancer

colon cancerDeath as a result of colon cancer occurs more than 50,000 times a year in the United States . It is the second leading cause of cancer death despite the fact that it is to a large extent preventable.  Because it has been shown that an individual’s susceptibility to colon cancer is partly determined by his or her genetic makeup, genetic testing for colon cancer can detect the disease early and save lives.   Physicians agree that everyone should be screened for the disease, but the specific screening recommendations vary depending on an individual’s risk.  A person without any genetic abnormalities pertaining to colon cancer has a lifetime risk of developing colon cancer of about 5%, while a person with a defined hereditary colorectal cancer syndrome may have a lifetime risk of 75% to more than 90%, depending on with which specific colorectal cancer syndrome he or she is afflicted.  To further complicate matters, some colon cancers have a tendency to run in families but are not part of a syndrome in which a specific genetic defect has been identified.  With these nonsyndromic family histories, the risk of colon cancer correlates with how many relatives are affected, how closely related they are (with first degree relatives conferring higher risk), and how old they were at the time of diagnosis.  A person with a family history of colon cancer in even one first degree relative (parent, sibling, or offspring), has a lifetime risk for colon cancer of 10%-15%, even higher if that cancer occurred before the age of 45 or if there is another family member affected. The current screening recommendation for people that have one first degree relative with colon cancer (or an adenomatous colon polyp, which is generally regarded as the same disease) is to begin screening at age 40, or ten years younger than the affected family member, whichever is earlier.

Although the role of genetic testing in colon cancer is important, less than 5% of colorectal cancers belong to a category of a defined hereditary colorectal cancer syndrome than can be identified directly through genetic testing.  This is partly because all of the genetic influences have not yet been described, nd partly because non-genetic factors are also involved. Dietary and environmental factors are likely important contributors. Specifically, the consumption of higher proportions of fruits, vegetables, and dietary fiber are associated with less risk of colon cancer, while consumption of fat,  ared meat, tobacco and alcohol are associated with a higher risk. An association does not prove cause and effect, however, so the role of many of these factors and others, such as vitamins and supplements, is still being worked out.

The genetics of colorectal cancer is not simple.  There are at least fifteen genes of four different categories with the potential to contribute to the development of colon cancer.  Functions of these genes include suppressing the growth of abnormal colon cells, helping cells repair or removing old unhealthy cells, repairing improperly replicated DNA, and removing damaged DNA.  Moreover, a single mutation will not usually directly result in cancer. In most cases it takes multiple mutations to induce colon cells that are unstable and proliferate aggressively. These random mutations occur over time; in fact, it may take as long as fifteen years for a normal cell to progress to an adenoma (polyp) and then to cancer.

For the hereditary syndromes, however, this is not the case.  In these syndromes, colorectal cancers (and many other types of cancers, such as uterine, ovarian, stomach, and urinary tract) develop much more quickly. For this reason the screening and surveillance recommendations are different, and genetic testing is available to help guide patients and their families to determine how to manage their increased risk.

The two predominant syndromes for which genetic testing is available are Familial Adenomatous Polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC, also called Lynch Syndrome).  FAP accounts for less than 1% of all colon cancers, but nearly 100% of the patients with this syndrome develop colon cancer.  Evaluation of this condition includes genetic testing, flexible sigmoidoscopy starting as young as 10-12 years of age, colon removal when polyps begin to form, and periodic upper endoscopy for tumors that may arise in the small bowel (an attenuated form of this condition is approached slightly differently). HNPCC is more common and accounts for about 3%-5% of all colorectal cancers.  Patients with this syndrome have a lifetime risk of cancer of about 80% and require early and frequent surveillance for not only colorectal cancer, but also gynecologic and urinary tract malignancy. Before genetic testing is decided upon, HNPCC is usually suspected by a set of clinical criteria describing a family tree of the malignancies.

Genetic testing for FAP is commercially available and includes testing for mutation in the APC gene and the MYH gene if the APC mutation is not present.  Genetic testing for HNPCC is guided by the evaluation of the tumor itself, if available, or by clinical criteria as previously mentioned, and includes looking for mutations in the MLH1, MSH2, and MSH6 genes.

The genetic tests, of course, are not completely accurate or conclusive.  A diagnosis of a family cancer syndrome results in intensive, expensive, and repetitive medical evaluation by multiple practitioners, but can be lifesaving and is therefore made with great deliberation and care.  Genetic test results, both positive and negative, require interpretation in the context of the patient’s presentation and family history.  Furthermore, the awareness of a genetic predisposition to disease has many implications for family, finance, insurance, and employment.   It is therefore recommended that a trained genetic counselor meet with the patient and family prior to a decision regarding specific genetic testing.

So you should discuss with your doctor how to go about being screened for colon cancer. You should disclose to your doctor any family history of colon cancer or colon polyps. You should discuss the role of genetic testing if you have more than one relative with colon cancer or polyps.  In 2012, you should not concede to the possibility of colon cancer.   It is preventable.

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