APC I1307K


What is APC I1307K?

Adenomatous polyposis coli is a tumor-suppressing gene that plays an important role in the carcinogenesis of colorectal cancer. If the APC gene is defective it fails to suppress colon cancer development. The mutation appears to make the gene unstable and prone to acquire mutations during normal cell division. The APC I1307K mutation is found in Ashkenazi Jews and has not been found in anyone who is not of Ashkenazi descent. This gene mutation causes a substantial increase in the risk of colorectal cancer (approximately 18–30% lifetime risk). Studies of APC I1307K are ongoing to better understand its role and implications.


In 1997, a Johns Hopkins research team found an inherited genetic mutation called APC I1307K. This mutation is found primarily in people of Ashkenazi Jewish heritage (Jews of Eastern European or Russian ancestry). Researchers believe that 6% of the Ashkenazi Jewish population carries this gene mutation, which gives them a significantly increased risk of developing colorectal cancer.

Both the APC I1307K mutation and mutations that cause FAP occur in the same gene, the APC (adenomatous polyposis coli) gene. The APC I1307K mutation is different from other APC mutations because the mutation itself does not cause colorectal cancer. Instead, this particular mutation creates an unstable spot in the gene that makes the gene more susceptible to additional genetic changes that may, in turn, lead to colorectal cancer.


How Is the APC I1307K Mutation Inherited?

People with the APC I1307K gene mutation have a 50% chance of passing the gene mutation to each of their children. Children who do not inherit the gene mutation cannot pass it to their own children.

Fig. 1 Example pedigree of APC I1307K Mutation

  1. George has colon cancer and carries the APC I1307K gene mutation.  His wife, Susan, does not have the gene mutation.  They have three children, George, Jr., Stephen, and Carol.  All were at 50 percent risk of inheriting the APC I1307K gene mutation from George.  In fact, both George, Jr., and Carol do carry the mutation and both have developed polyps.
  2. George, Jr., and his wife, Connie, have two children.  Both children had a 50 percent chance of inheriting the gene mutation.  Their daughter, Alice, is affected.
  3. Stephen and his wife, Gloria, have two children.  Because Stephen does not have the gene mutation, his children had no risk of inheriting the gene mutation from him.
  4. Carol and Bill have three children.  Each child had a 50 percent chance of inheriting the gene mutation from Susan.  Peter and Sally carry the gene mutation, but neither one has yet developed polyps or colon cancer.

    *Children who do not inherit the gene mutation cannot poass it to their own children.


Why Is This Mutation Most Common in People of Ashkenazi Jewish Descent?

Recent scientific studies tell us that certain groups of people, including Ashkenazi Jews, have unique genetic mutations that increase their risk of certain cancers or diseases. In most cases, doctors who study genetics believe that the first time a gene change occurs in a group of people, it occurs by chance. When this group is small and separate from other groups, by geography or culture, for example, the gene change may become more frequent from one generation to the next. This is probably why the APC I1307K gene mutation is most commonly found in people of Ashkenazi Jewish descent.


Diagnosing APC I1307K - Genetic/DNA Testing

There is a gene test to look for this inherited gene mutation.

Fig 2. Chromosome 5 showing APC I1307K


Who Should Consider Testing for the APC I1307K Mutation?

Any person of Ashkenazi heritage who has a personal or family history of colorectal cancer or colorectal polyps may wish to consider testing. A family history means having at least one close family member with colorectal cancer or polyps. Ashkenazi Jews without a family history of colorectal cancer may still wish to obtain genetic counseling to learn the value of gene testing in their own unique circumstances.

Genetic counseling is available, and recommended, for individuals who may have the APC I1307K mutation, and their family members. Genetic counselors will explain the inheritance pattern of APC I1307K, discuss which family members are at risk for developing the condition and provide necessary information regarding genetic testing. Counseling services are available through genetic and oncology departments in many hospitals. To make an appointment with a member of the Johns Hopkins professional medical team or to speak with someone at the Colorectal Cancer Risk Assessment Service, please call (410) 614-LIFE (5433). Also, it is recommended that APC I1307K families contact registries for access to resources and for help with identification of at-risk family members.


What Should You Do if You Receive a Positive Gene Test Result?

It is important to detect colon polyps or cancer early. Routine screening is the best way to do this. At this time, experts recommend the following:

Persons with a positive test result, who do not already have colon cancer or polyps, should have a routine colonoscopy every 2 years beginning at age 35 OR 5–10 years before the earliest age at which colon cancer or polyps occurred in the family, whichever is younger.

Patients with a personal history of colon cancer or polyps should have a routine colonoscopy every 2 years, or more often at the recommendation of their doctor.

Relatives of people testing positive for this gene mutation should consider counseling and testing as well.


Genetic Testing and Insurance

With any gene test there is a risk of insurance (life or health) or employment discrimination. At this time there are federal laws that offer protection against discrimination of people who have medical insurance through a group health plan. Some states have laws to protect people, but the laws on insurance and employment discrimination vary from state to state. The Americans with Disabilities Act may protect people with a positive gene test from discrimination in the workplace. These issues can be discussed with a genetic counselor.


Symptoms 

Many patients with colorectal cancer experience no symptoms in the early stage of their disease. In fact, many people have no symptoms until the disease is quite advanced. Therefore, routine colorectal screening and an appreciation of risk factors are extremely important.

Since many of the symptoms of colorectal cancer are also symptoms of a variety of other colon diseases, it is important to see your physician so that the necessary tests can be run and a diagnosis made.

The following is a list of symptoms that may occur:

• Blood in the stool
• Diarrhea that is not the result of diet or illness
• A long period of constipation
• Crampy pain in the abdomen
• Change in bowel habits
• Persistent decrease in the size or caliber of stool
• Frequent feeling of distention in the abdomen or bowel region(gas pain, bloating,  fullness, with or without cramping)
• Weight loss with no known reason
• Vomiting and continual lack of energy


In addition to polyps, abnormalities in other areas of the body may give early clues to the presence of FAP. These abnormalities may include bumps or lumps on the bones of the legs, arms, skull, and jaw; cysts of the skin; teeth that do not erupt when they should; and freckle-like spots on the inside lining of the eyes.

It should be emphasized that there is no safety in simply waiting for symptoms to develop. It is vital that parents and guardians make every effort to have examinations of their children starting at age 11 even if they do not have symptoms.

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