For you and your family: Genetic risk and colorectal cancer

Screening for colorectal cancer saves lives. But what if you had a crystal ball that tells whether you and your family are more likely to face the disease? Unfortunately, we don’t have a crystal ball—or its medical equivalent—quite yet, but you can get some insight by knowing your family medical history and whether you have any hereditary genetic conditions like Lynch or FAP syndromes that may increase your risk of colorectal cancer.

How is cancer caused genetically?

While there remains much to learn about this disease, we know it is caused by gene mutations, or changes, that result in cells growing out of control. As you age, gene mutations accumulate, and this is why colorectal cancer most often happens in people over age 50. In most cases, the gene mutations leading to cancer happen sporadically—or at random—although they can be helped along by carcinogens, like the chemicals in cigarette smoke.

Yet in about 25 percent of cases patients have a family history of the disease, signaling a possible genetic condition that causes mutations and increases the likelihood of colorectal cancer at a younger age.

Genetic mutations that increase the risk of cancer can be inherited from parents. Inherited genetic mutations play a role in 5 to 10 percent of all cancer cases, as well as colorectal cancer. Researchers have found more than 50 hereditary cancer syndromes overall. Fortunately, a number of these inherited conditions can be identified through genetic testing, and the results can be life saving.

What are the genetic risks of colorectal cancer?

Knowing whether you’re at increased risk of genetic mutations that can cause colorectal cancer can help you take precautions to avoid the disease. These are the inherited genetic syndromes  relevant to colorectal cancer:

• Familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and Gardner syndrome
• Lynch syndrome (hereditary non-polyposis colon cancer, or HNPCC)
• Peutz-Jeghers syndrome
• MYH-associated polyposis (MAP)
• Li-Fraumeni Syndrome

Here is a more detailed explanation of the two most common genetic syndromes associated with increased risk of colorectal cancer:

What is Lynch Syndrome?

About three to five percent of colorectal cancers are believed to be caused by mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. When someone carries a harmful mutation in any of these genes, they have a condition called Lynch Syndrome, which is also called Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome.

People with Lynch syndrome are at higher risk of developing several different types of cancer, in addition to colorectal cancer:

• Endometrial (uterine) cancer
• Ovarian cancer
• Gastric (stomach) cancer
• In addition, rarely, urinary tract, renal/pelvic, biliary tract, small bowel, pancreatic, and brain cancers

Some people with Lynch syndrome may also develop sebaceous adenomas, which are noncancerous tumors of an oil-producing gland in the skin.

What is FAP Syndrome?

People with the classic type of familial adenomatous polyposis (FAP) may begin to develop multiple non-cancerous growths, or polyps, in the colon as early as their teenage years (screening usually begins at age 8 to 10 years).

The type of polyp most often seen in FAP syndrome, called an adenoma, is precancerous and has the potential to develop into cancer. Unless these growths are removed, they may become malignant, or cancerous. The average age at which an individual develops colon cancer in classic FAP is 39 years. In people with classic FAP, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon.

Some people have a variant of the disorder, called attenuated familial adenomatous polyposis (AFAP), which develops fewer polyps. The average age of colon cancer onset for those with AFAP is 55 years.

How do I know if I’m at risk?

There are three subgroups of risk for cancer–sporadic, familial, and hereditary. If you fall into the sporadic group, which means you have no family history of cancer or inherited genetic predisposition, you have about a 1 in 23 chance of getting colorectal cancer. If you have familial risk, meaning an immediate family member has the disease, your lifetime risk increases to 10 to 20 percent.  

Those who have the highest lifetime risk of colorectal cancer are in the hereditary subgroup. Depending on the particular genetic syndrome, the chances of getting colorectal cancer may be 30 to 100 percent.

Special genetic tests can find gene mutations linked to these inherited syndromes. A healthcare provider can help you identify your risk and which type of genetic tests, if any, may be useful. Genetic testing is typically conducted with either a blood or saliva draw and completed in a lab.

What can I do after I know my genetic risk?

Colorectal cancer is one of the most preventable and treatable forms of cancer when it’s found early. Screening is the most important thing you can do to prevent colorectal cancer because it finds cancer in the early stages, before it even has the chance to grow or develop. Talk to your healthcare provider about which screening methods are right for you and when you should begin screening.