Southwest Women’s Oncology performs these genetic tests in our office to help determine your predisposition to gynecologic cancer or known genetic mutations that may be candidates for prophylactic surgery.
Genetic tests run by Southwest Gynecologic Oncology Associates include:
Endometrial cancer is the second most common type of cancer in patients with HNPCC mutations. Patients with HNPCC mutations need to be screened more aggressively for endometrial cancers, breast cancers, skin cancers, and many other cancers. With endometrial cancer, the gynecologic oncology physician may recommend an early hysterectomy as prophylaxis.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common known hereditary cause of colon cancer. In fact, HNPCC accounts for between two and five percent of all colon cancer cases.
HNPCC is a hereditary syndrome that is caused when a person inherits a mutation in one of five different genes. If people born with HNPCC do not undergo early and regular screening, they have a much higher risk of developing colon cancer than the general population if they do not undergo early and regular screening.
About two to five percent of all colon cancer cases are attributed to HNPCC, also called Lynch Syndrome, after Dr. Henry Lynch who realized that it was a separate disorder from other hereditary colon cancer syndromes.
Certain things are misleading about the name of the syndrome — hereditary nonpolyposis colon cancer. First, HNPCC is not a form of cancer, but only a syndrome that puts people at high risk for colon cancer. Second, even though the name has nonpolyposis in it, people with HNPCC will still develop colon polyps as a precursor to colon cancer. Scientists simply use this term to distinguish HNPCC, which causes a small number of polyps to develop, from another hereditary colon cancer — familial adenomatous polyposis syndrome — in which thousands of polyps develop.
BRCA1 and BRCA2
BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumor suppressors.
In normal cells, BRCA1 and BRCA2 help ensure the stability of the cell’s genetic material (DNA) and help prevent uncontrolled cell growth. Mutation of these genes has been linked to the development of hereditary breast and ovarian cancer.
The names BRCA1 and BRCA2 stand for breast cancer susceptibility gene 1 and breast cancer susceptibility gene 2, respectively.
How do BRCA1 and BRCA2 gene mutations affect a person’s risk of cancer?
Not all gene changes, or mutations, are harmful. Some mutations may be beneficial, whereas others may have no obvious effect.
Harmful mutations can increase a person’s risk of developing a disease, such as cancer.
A woman’s lifetime risk of developing breast and/or ovarian cancer is greatly increased if she inherits a harmful mutation in BRCA1 or BRCA2. Such a woman has an increased risk of developing breast and/or ovarian cancer at an early age (before menopause) and often has multiple, close family members who have been diagnosed with these diseases.
Harmful BRCA1 mutations may also increase a woman’s risk of developing cervical, uterine, pancreatic, and colon cancer. Harmful BRCA2 mutations may additionally increase the risk of pancreatic cancer, stomach cancer, gallbladder and bile duct cancer, and melanoma.
The likelihood that a breast and/or ovarian cancer is associated with a harmful mutation in BRCA1 or BRCA2 is highest in families with a history of multiple cases of breast cancer, cases of both breast and ovarian cancer, one or more family members with two primary cancers (original tumors that develop at different sites in the body), or an Ashkenazi (Central and Eastern European) Jewish background.
However, not every woman in such families carries a harmful BRCA1 or BRCA2 mutation, and not every cancer in such families is linked to a harmful mutation in one of these genes. Furthermore, not every woman who has a harmful BRCA1 or BRCA2 mutation will develop breast and/or ovarian cancer.
According to estimates of lifetime risk, about 12.0 percent of women (120 out of 1,000) in the general population will develop breast cancer sometime during their lives compared with about 60 percent of women (600 out of 1,000) who have inherited a harmful mutation in BRCA1 or BRCA2. In other words, a woman who has inherited a harmful mutation in BRCA1 or BRCA2 is about five times more likely to develop breast cancer than a woman who does not have such a mutation.
Lifetime risk estimates for ovarian cancer among women in the general population indicate that 1.4 percent (14 out of 1,000) will be diagnosed with ovarian cancer compared with 15 to 40 percent of women (150–400 out of 1,000) who have a harmful BRCA1 or BRCA2 mutation.
It is important to note, however, that most research related to BRCA1 and BRCA2 has been done on large families with many individuals affected by cancer. Estimates of breast and ovarian cancer risk associated with BRCA1 and BRCA2 mutations have been calculated from studies of these families.
Because family members share a proportion of their genes and, often, their environment, it is possible that the large number of cancer cases seen in these families may be due in part to other genetic or environmental factors. Therefore, risk estimates that are based on families with many affected members may not accurately reflect the levels of risk for BRCA1 and BRCA2 mutation carriers in the general population.
In addition, no data are available from long-term studies of the general population comparing cancer risk in women who have harmful BRCA1 or BRCA2 mutations with women who do not have such mutations. Therefore, the percentages given above are estimates that may change as more data become available.
Are genetic tests available to detect BRCA1 and BRCA2 mutations, and how are they performed?
Yes, there are tests. Several are available for BRCA1 and BRCA2 mutations (14). Most of these methods look for changes in BRCA1 and BRCA2 DNA. At least one method looks for changes in the proteins produced by these genes. Frequently, a combination of methods is used.
How are they performed? A blood sample is needed. The blood is drawn in a laboratory, doctor’s office, hospital, or clinic and then sent to a laboratory that specializes in the tests. It usually takes several weeks or longer to get the test results. Individuals who decide to get tested should check with their health care provider to find out when their test results might be available.
Genetic counseling is generally recommended before and after a genetic test. This counseling should be performed by a health care professional who is experienced in cancer genetics.
Genetic counseling usually involves a risk assessment based on:
• The individual’s personal and family medical history and discussions about the appropriateness of genetic testing
• The specific test(s) that might be used and the technical accuracy of the test(s)
• The medical implications of a positive or a negative test result
• The possibility that a test result might not be informative (an ambiguous result)
• The psychological risks and benefits of genetic test results, and
• The risk of passing a mutation to children.