Inherited Cancer

Testing for Inherited Cancer

If you have a family history of cancer, particularly cancers that occur before age 50, you may want to explore genetic counseling to determine if an inherited gene mutation could be responsible. Hereditary cancers are not always obvious. A mutation that leads to breast cancer in your grandmother may lead to ovarian cancer in your aunt. Likewise, a mutation that causes colon cancer in your sister may cause endometrial cancer in your daughter.

To determine whether your family's cancers might be hereditary in nature, a genetic counselor will need to know medical details about the family, especially those who have been diagnosed with cancer. Age of diagnosis and the exact diagnosis is the most important factors; be prepared for a counselor to request medical records. Also be prepared for several possible conclusions about your family history:

• The cancers in the family, even if there are several, may be "sporadic" and not linked to an inherited genetic defect.
• The pattern fits a known hereditary cancer syndrome for which genetic testing is available. Those who test positive for the mutation would need to be vigilant about prevention and screening measures.
• Family history suggests an inherited pattern, but one that fits no currently characterized syndrome. Everyone who may have inherited the apparent predisposition to cancer should pursue stepped-up prevention and screening efforts.

Some inherited cancer syndromes for which testing is available are

• Hereditary breast and ovarian cancer syndrome, caused by mutations in the BRCA1 or BRCA2 genes, often referred to as the "breast cancer genes."
• Hereditary non-polyposis colon cancer, caused by mutations in the MLH1 and MSH2, genes. Such mutations are also linked to cancers of the endometrium, stomach, small bowel, ureter, ovary and collecting system of the kidneys.
• Familial adenomatous polyposis, caused by a mutation in the APC gene that leads to the growth of hundreds or thousands of polyps in the colon beginning as early as the teenage years.
• Ataxia telangiectasia, a complex disorder caused by a mutation in the ATM gene. Among other effects, including dysfunction of the cerebellum (the part of the brain that controls motor function and balance), A-T has been linked to lymphomas and leukemia. This autosomal recessive disorder is diagnosed in childhood. As individuals live longer, other cancers have been observed, including ovarian and breast cancers, stomach cancer and melanoma.
• Multiple endocrine neoplasia 1 and 2 are two separate rare disorders caused by mutations in the MEN1 or RET genes, respectively; MEN1 or 2 can lead to cancer in one of the endocrine glands, such as the parathyroid, thyroid, pancreas, pituitary or adrenal gland.
• Researchers also suspect a hereditary component to some cases of prostate and lung cancer, but as yet have not identified gene mutations for testing.

The genes themselves don't cause cancer. The problem comes when they are not functioning normally. You were born with two copies of each of these genes, one inherited from your mother and one from your father. In some cases, if you inherit a mutation in one of these genes, you will not immediately develop cancer, because you have a backup functioning gene. But over time, the unaffected gene may become damaged in one cell, allowing that cell to become cancerous and multiply.

Such an outcome is common among individuals with an inherited mutation linked to breast cancer or colon cancer. Those with a BRCA mutation face a lifetime breast cancer risk of up to 85 percent, compared to about 12.5 percent in the general population, and a lifetime ovarian cancer risk of up to 44 percent, compared to a population risk of about one percent.

A positive result from a genetic test does not mean you will definitely develop one of these cancers, only that your risk is much higher than that of individuals without a mutation. And a negative test result certainly does not mean you won't develop cancer. In fact, only one out of 10 cases of breast cancer involves an inherited mutation, and only five to 10 percent of colon cancers are hereditary.

The knowledge that you are positive for a mutation allows you to take action to reduce your risk through preventive measures, such as more frequent screening to detect early growths or tumors, taking protective medications, or even prophylactic surgery to remove the organ prone to cancer.