Cancer colon hereditary

Even with a genetic mutation, you can avoid colon cancer.

A large number of Americans are at higher risk for colon cancer than the general public. Fortunately, the vast amount of genetic information uncovered in recent years allows counselors and clinicians greater knowledge, and a more accurate means, of predicting an individual's genetic risk for developing colon cancer.

Genetic counselors can help people assess their personal risk for developing colon cancer and make important early screening recommendations that may save lives. We spoke with Karen Johnson, M.S., Certified Genetic Counselor, at the Cancer Risk Assessment Program at Johns Hopkins--one of the leading cancer genetic research centers in the country.

Q: Who should be referred to a clinic like Johns Hopkins for genetic counseling?

A: Anybody who has multiple family members who were diagnosed with colon cancer. Anybody who has a family member who was diagnosed with colon cancer at a particularly young age--we consider under the age of 50 to be relatively young for a colon cancer diagnosis. Anybody who is concerned about their cancer risk can benefit from information. Even if I in turn say you are at no higher risk than anyone in the general population and here's what you should be doing, having that kind of reassurance can reduce a lot of anxiety for many people.

Q: How has our understanding of familial colon cancer changed in the last few years?

A: Before about 1992 or 1993, we recognized the fact that in families where there are multiple family members with colon cancer, there was a greater risk for other family members to develop cancer, but we didn't know specifically what the reason was. Within the past few years, we have been able to identify certain genes that we know are associated with colon cancer syndromes. In some families where there is a strong family history of cancer, it is possible to look at the genetic makeup of those individuals--say, for example, an individual who is diagnosed with colon cancer at an early age--and determine if there is a change in one of those genes that can be associated with colon cancer. If we find that change, we know what to test other family members for. Say, for example, your dad had a change in one of these genes that caused him to get colon cancer. We could test you to see if you carried that same gene change. If you didn't, we know that you are at the general population risk and we can give you screening recommendations for the general population. But if you did inherit that gene change, we know that your risk is much higher and we can be intensive in our surveillance and what we recommend for screening for you. This is to help clarify within families where there is a family history which individuals are at high risk and which people don't need to be as concerned.

Q: Is there a blood test available to determine if you did inherit a specific gene mutation?

A: All genetic testing is done through a blood test, but the tests are not routinely offered to everybody with a family history of colon cancer. We are really looking for specific features that we know go along with each of these genes. We are at the infant stage right now of our understanding. Like I said, it has really only been in the last five to six years that we have known anything about the genetics of the inherited forms of colon cancer. For some families, it is very obvious that their history is probably associated with a certain gene and testing would be available. But it really requires that you have someone like a genetic counselor sit down and look through your whole family history to help determine if, yes, it is appropriate or, no, it is not something that you need to be worried about at this point because it is not going to give you any additional information.

Q: What should a person look for in their family tree?

A: We are looking for multiple family members with colon cancer, usually three or more family members who have been diagnosed.

Q: First-degree relatives?

A: There needs to be three or more affected members in the family, and they should be first-degree relatives to each other. For example, your mom, her sister, and her mother had colon cancer. Your aunt and your grandmother are not your first-degree relatives, but they are first-degree relatives to your mom. They are three relatives who are closely related to each other. We are looking for multiple generations of a family to be affected. In the previous case, your grandmother, your mom, and a sister had colon cancer, too, so it looks like the disease is being passed through the family.

We are looking for young ages. For any family with members diagnosed with colon cancer under age 50, we start to think about the idea of genetic testing.

We look for family members who have been diagnosed with multiple, multiple colon polyps--someone who has, for example, had 100 colon polyps. There is a genetic condition associated with multiple polyps, and testing is available for that.

And in some families, we know that there can be actually an association with other cancers. Colon cancer can be seen with uterine cancer and with ovarian cancer. If we see those kinds of clusterings in a family, it also makes us think about the idea of possibly pursuing genetic testing.

There is one specific gene mutation that has been identified in the Askenazi Jewish population, so for people who have a history of colon cancer and are of Jewish descent, testing is available to them, as well.

Q: If, for example, someone has the blood test and it is positive for the genetic mutation, will they definitely get colon cancer? And if not, what percentage will?

A: It varies, depending upon what mutation we find. Mutations in at least six different genes can be associated with colon cancer risk. For one condition that we call familial polyposis, where we see people with hundreds of colon polyps, if they have a mutation in the gene associated with that condition, there is a 100 percent lifetime risk of developing colon cancer--obviously, very, very high.

For people who have mutations associated with a condition that we call hereditary nonpolyposis colon cancer, the lifetime risk is about 80 percent. It's still high, but it's not the 100 percent that goes along with familial polyposis.

For people who have the mutation that we see in the Jewish population, the risk is closer to about 20 to 30 percent.

Gradients of risk vary, depending upon what mutation is present in your family.

Q: Would you please define these two types of hereditary cancers--the familial and the hereditary? First, familial.

A: The full name is familial adenomatous polyposis; people use the abbreviation FAP, usually, in referring to it. FAP is a condition in which people develop hundreds to thousands of polyps in their colon and GI tract. It does carry about a 100 percent lifetime risk for developing colon cancer. It is associated with mutations in a gene we call the APC gene. There are some extracolonic things that go along with the condition, including the presence of bony tumors on the jaw, the skull, or limbs. We can see cysts on the skin, problems with the teeth where the teeth don't erupt the way that they are supposed to, benign changes on the retina of the eye, or possibly fibrous tumors in the abdomen. These are all factors that clue us in to the possibility this is probably the condition that is in the family. But the classic, clinical feature of FAP is the hundreds and thousands of colon polyps.

Q: And the second form?

A: It's HNPCC--hereditary nonpolyposis colorectal cancer, where we can see earlier onset of colon cancer. The average age is in the early 40s--about age 44--but we can see people as young as their 20s being diagnosed with colon cancer. In this condition, we can see the association with other cancers--the most common being uterine cancer in women, but also ovarian, stomach, and small intestine, as well as cancers of the urinary tract and of the bile ducts. When we start to see clusterings of all those cancers together, it leads us to think about HNPCC. The predominance of the colon cancers that occur are what we consider to be right-sided colon cancers, occurring in the cecum area or the ascending colon section, though we don't really know the reason for that, yet. There are actually now five genes that we know are associated with HNPCC. An individual who has a mutation in any of those five genes has about an 80 percent lifetime risk of developing colon cancer.

Q: If a person looks at their family tree and does not see a cluster of colon cancer but does discover uterine or ovarian cancers, then they should be concerned?

A: It should raise a flag. Maybe they need to speak to someone.