Most cancers occur by chance or sporadically. Scientists also have discovered that there are specific inherited factors, or genes, that can contribute to the development of some forms of breast, ovarian, colorectal, prostate and other types of cancer. This section will provide explanations of the following.

• Role of Genes
• Genetic Counseling and Testing
• Most Common Hereditary Cancer Types

Role of Genes

Some people may develop cancer due to alterations in hereditary factors called genes. Hereditary cancer is the development of cancer due to an inherited gene mutation (changes in a specific gene) that was passed from a parent to a child on conception. If a person has inherited such a gene mutation, he has inherited an increased risk to develop cancer in his lifetime, which is higher than the cancer risk of someone in the general population.

Genetic testing is now available for some of these types of hereditary cancers. People who are interested in learning whether or not they have an increased likelihood of developing certain cancers or whether they inherited a gene that contributed to their own or a family member’s cancer, should consult with a specialist in the area of hereditary cancer, cancer risk assessment and genetic counseling and testing.

top

Genetic Counseling and Testing

Genetic counseling involves a discussion of your personal and/or family history of cancer. Some families inherit the predisposition to develop a specific type of cancer, which can develop at an early age. This is caused by a specific mutation that may be detected by specialized laboratory analyses. The goal of cancer genetic counseling is to provide you with clear and clinically relevant information about genetic risk factors in terms you can understand.

Genetic testing involves the use of laboratory methods to obtain a more precise estimate of your cancer risk. Deciding whether or not to have genetic testing is a personal choice that can be made at the time of the counseling session or at a future date.

Genetic counseling does not require genetic testing. Genetic testing may not be useful for everyone receiving genetic counseling. Genetic consultation to determine the risk and benefits of testing for specific genes predisposing to cancer and to interpret the results of these tests is provided by Carmen B. Lozzio, MD, clinical geneticist, and Teresa Blake, MS, genetic counselor.

For appointments and information concerning these services, please call 865.305.6485 or 800.325.3894.

top

Most Common Hereditary Cancer Types

The following types of cancer have known hereditary risk factors in a certain percentage of affected persons and their close relatives.

Breast and Ovarian Cancer

It is known that one of every 10 women will develop breast cancer during her lifetime and one in 50 will develop ovarian cancer. Most cancers are not hereditary. However, about 5 to 10 percent of breast cancer and 10 percent of ovarian cancers are due to inherited susceptibility hereditary predisposing factors. The majority of the cases with hereditary breast and/or ovarian cancer cases have mutations within two specific genes: BRCA1 and BRCA2. In addition, some specific mutations are more prevalent in certain ethnic groups. For example: one in 40 persons of Eastern European Jewish (Ashkenazi) descent carry one of several specific BRCA1 or BRCA2 mutations.

The following are increased genetic risk factors indicating the need for counseling and possible testing for BRCA1/BRCA2 mutations.

• Family history of two or three more close relatives from the same side of the family who have had breast and/or ovarian cancer
• At least one close relative with breast cancer prior to age 50 or one with ovarian cancer at any age
• Breast cancer under age 50
• Breast and ovarian cancer in the same person
• Breast or ovarian cancer in Jewish women with Jewish descent
• A male family member with breast cancer

Some of the basic principles in breast/ovarian cancer counseling can be summarized as follows.

• Hereditary breast and/or ovarian cancer are dominantly inherited conditions. This means that a mutation genetic susceptibility to breast/ovarian cancer can be inherited from men as well as women. Men may not develop male breast cancer but could suffer other forms of cancer such as prostate cancer or be free of cancer and still transmit the gene to their daughters or through their sons to the granddaughters. Therefore, when a person has a mutation, there is a 50 percent chance that this mutation will be passed on to each of their children regardless of gender.
• Each gene has many different types of mutations and half of the families with BRCA1 or BRCA2 mutations have a unique mutation specific for that family. This is why it is best to test a family member that has had cancer to identify the specific mutation in the family and all the relatives at risk can be tested later for this specific mutation only.
• The initial analysis for detection of BRCA1 and BRCA2 mutations involves complete sequencing of both genes, and this type of test is very costly. Once a specific mutation is identified, the test for that specific mutation is less expensive because it only requires the analysis of one mutation.
• Insurance often covers 80 to 100 percent of the charges associated with genetic testing. Prior to any testing, the UT Medical Center staff will assist in obtaining information concerning eligibility, coverage and specific requirements from each insurance carrier.
• Women who carry a BRCA1/BRCA2 mutation do not automatically get cancer but are at greater risk than other women for developing cancer earlier in life. Preventative and screening measures should be started earlier and more frequently than in the general population.
• Women who do not carry the BRCA1/BRCA2 mutation identified in her family are at the same risk as the general population for nonhereditary breast or ovarian cancer. They should follow the same screening proposed for all women (monthly self-breast exam and annual clinical exams and mammograms after age 40).
• Individuals affected with breast or ovarian cancer and have a high-risk family history but who have negative results for BRCA1/BRCA2 mutation testing may carry a mutation for a gene that has not yet been discovered. These families have a higher risk of developing breast or ovarian cancer than the general population.

Colon Cancer
There are two main types of hereditary colon cancer.

Familial Colon Adenomatosis Polyposis—Familial adenomatosis polyposis (FAP) is a dominantly inherited disorder causing multiple polyps of the colon and that these colon polyps precede the development of colorectal cancer. FAP is associated with a mutation in the specific gene called Adenomatosis Polyposis Coli (APC). Generally individuals with FAP are diagnosed around the age of 40 years. However, colon cancer associated with FAP may occur from late childhood to old age. The same APC gene can cause Gardner Syndrome. The symptoms of Gardner Syndrome can include polyps in the upper gastrointestinal tract (stomach and small intestine), pigmented lesions in the eye that may be found before the polyps, tumors in the jaw or skull and benign tumors or cysts containing lipids that may appear in the back.

Testing for mutations in the APC gene mutation is available and should include genetic counseling by geneticists professionals trained in the field of genetics. It is important to realize that negative results only are significant if a specific mutation has been detected in an affected member of the family. In this situation, the results of the test can help reduce the frequency of follow-up sigmoidoscopy in the members of an affected family who have not inherited the mutation. For individuals identified with FAP, colectomy in those with polyps is the treatment of choice. Also, use of anti-inflammatory drugs and aspirin on a regular basis appears to lower the relative risk of colorectal cancer, and annual sigmoidoscopy is recommended in those who carry the mutation. Consult with your physician to determine the most appropriate management of your diagnosis.

Hereditary Nonpolyposis Colorectal Cancer—Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary colon cancer syndrome. This dominantly inherited disease is associated with increased risk for colorectal and endometrial cancers. This syndrome has been associated with mutations in six DNA mismatch repair genes. The most common are hMSH2 and hMLH1. Molecular analysis of hMSH2/hMLH1 genes requires sequencing of the genes.

Genetic testing for mutations in the MSH2 and MLH1 genes currently is available. Members of affected families with the mutation are offered intensive surveillance and consideration for prophylactic surgery. Family members without the mutation found in their family can be followed with the same surveillance recommended for the general population. Thus, a correct interpretation of the results of these tests is very important to recommend the appropriate management of each case.

Other Types of Genetically Linked Cancer

• Li-Fraumeni Syndrome (Leukemia, Sarcoma, Brain, Breast, Adrenal)
• Von Hippel-Lindau (renal Carcinoma, Hemangiomas, Pheochromocytoma)
• Multiple Endocrine Neoplasia I (Parathyroid, Pancreas, Pituitary)
• Multiple Endocrine Neoplasia II (Thyroid, Pheochromocytoma, Parathyroid Adenoma)
• Neurofibromatosis

top