Genetic Testing For Cancer Risk


Testing for gene abnormalities can identify a patient who carries an inherited tendency to develop cancer. Genetic testing is done with the goals of preventing cancer and to save lives. A patient with increased risk for developing cancer can have preventative treatment such as risk reducing surgery.  Enhanced screening for cancer can be focused on patients with extra risk. Cancer can then be detected very early when it is easily cured. Genetic testing can be very expensive and so not everyone can be tested. Testing is usually recommended when a person has a known cancer with a high likelihood of an underlying genetic mutation, or when there is a strong family history of cancer that suggests a mutation is being carried by members of the family.  If any family member is known to carry a mutation predisposing to cancer, then other family members will qualify for testing, because they have a risk of carrying the same mutation.

Our DNA controls how each cell in her body will work, and what characteristics each cell can express.  Genes are the small sections of DNA that control the production of individual proteins, and those proteins carry out the processes inside the cells of the body.  DNA may be damaged, and the consequence may be that a gene may not control the usual processes. Defective genes can lead to disease, unusual traits, or development of cancer. Changes in the DNA are called mutations.  DNA is inherited from each parent. If the inherited DNA is abnormal then risk for disease or cancer is also inherited. Most of the genes associated with risk for cancer or genes that control the repair of DNA. These are also called tumor suppressor genes.  Examples of these genes include BRCA, p53, and Lynch syndrome genes.

Genetic testing can be done on a blood sample, a saliva sample, or occasionally on a tissue sample.  Dr. Martin has an intense interest in genetic testing and counseling to help protect patients from an inherited cancer risk.  

When testing was first available it was prohibitively expensive to test more than 1 or 2 genes.  Modern laboratory technology now allows dozens of genes to be tested as a panel for much lower cost than was previously charged for a single gene test.  The pattern of individual cancers that are present in a family may suggest a classic association with a particular gene abnormality, however many times a mutation is found that is either not associated with any of the cancers found in the patient with the family or is only associated with 1 or 2 of the many different cancers identified.  For this reason it is illogical to do single gene testing or testing for only a particular syndrome when there is known overlap with many of the genetic and disease patterns. For example, ovarian cancer is likely to occur for a patient with a BRCA mutation and is also likely to occur for a patient with a Lynch syndrome mutation. The same is true for breast cancer.  Up to 90% of all cancers occur in patients born without a genetic mutation, and their cancer developed from problems in the DNA that developed over a lifetime instead of from an inherited predisposition. Not every mutation that can predispose to cancer will always cause cancer.

Genetic counseling is the process of identifying patients who are suspected to carry a dangerous mutation, and includes the education of those patients regarding possible management to reduce their risk from a future cancer.  A genetics counselor can provide detailed statistics regarding the likelihood that a known mutation will progress to cancer and at what age groups that might occur. Recommendations can then be provided about what age to do testing, and what age to do preventative care.  A confirmed mutation has many implications for other family members who have not yet been tested. Many patients choose to have testing purely to benefit their children or their grandchildren.

Indications for testing:

Genetic testing is indicated for some patients who have already been diagnosed with cancer.  Some cancers have a known high incidence of underlying inherited mutations, such as ovarian cancer.  All ovarian cancer patients should be offered genetic testing. Some cancers are much more likely to have an underlying inherited mutation if they occur at a young age.  All endometrial cancer patients should be offered genetic testing if the cancer is diagnosed prior to age 45. Breast cancer patients with bilateral breast cancer or breast cancer at early age should also be advised to have testing.  The patient who has had several types of cancer is also highly likely to be a mutation carrier. Common example might be a patient with prior uterine cancer and now with colon cancer, or a patient with prior breast cancer who now develops ovarian cancer.  The patient who had breast cancer on two different occasions also has an increased risk of being a mutation carrier and should undergo testing.

Genetic testing is also indicated for family members of a patient who had a positive genetic test confirming a gene mutation.  If a patient has been confirmed to be a mutation carrier, then every first-degree relative such as a sibling, or child, or parent of that carrier has a 50% chance of carrying the same mutation.  A grandchild, or niece or nephew or aunt or uncle of a known carrier has a 25% chance of being a carrier of the known mutation. Testing is appropriate when there is a 25% chance of obtaining an abnormal test result.  

Genetic testing is also indicated when there is a cluster of cancers in the same family that are possibly related to a single gene abnormality.  Multiple people in the same generation or multiple generations of the family with cancer are often recognized and should be explored with genetic testing.  There may be many different cancers in the same family all because by the same mutation. Cancers that may be in a family cluster and related to inherited events cancer types that are associated with an inherited tendency and are often found in family cluster of cancers include ovarian cancer, breast cancer, colon cancer, prostate cancer, uterine cancer, and pancreatic cancer.  A doctor who treats cancer or a genetics counselor can recognize the abnormal family history and confirm that testing should be completed.

Genetic testing is indicated when another first or second-degree family member has already been confirmed to carry a mutation that is known to predispose to cancer.


Hereditary Breast and Ovarian Cancer syndrome describes families where multiple members have either breast or ovary cancer, or occasionally a patient who has had both of these cancers.  A single underlying mutation such as the BRCA gene mutations can predispose to both cancers. These patients may develop breast cancer at early age, have bilateral breast cancer, and have unusual numbers of patients in the same family who each had one of these cancers.  Breast cancer in a male patient is especially likely to be caused by an underlying BRCA mutation. By comparison, ovary cancer occurs in only about 2% of women without inherited risk. Breast cancer occurs in only about 8-10% of women without an inherited risk. It is therefore unusual to have 3 out of 4 family members in the same generation develop cancer of the same type.  Similarly, it is unusual to have a grandmother and aunt and mother with the same breast or ovary cancer. HBOC should be considered when breast cancer or ovary cancer occurs at or before age 45, or if breast cancer occurs before age 50 with other associated members in the family having cancer of the prostate, pancreas, or a melanoma. HBOC should be considered when a patient has both breast and ovarian cancer or when the patient has 2 separate breast cancers.  HBOC should be considered when breast and ovarian cancer occurs in multiple generations of the family. Remember that a father can pass along a genetic mutation for a future ovary or breast cancer even though the father may not have developed a cancer. A male with breast cancer is a strong reminder to consider HBOC.

The majority of HBOC families carry mutations of BRCA1 or BRCA2.  Women with breast cancer have a roughly 10-15% chance of carrying a BRCA mutation.  Women with a “ triple negative “ breast cancer and under the age of 60 may have up to a 30% chance of carrying a BRCA mutation.  BRCA mutation is otherwise rare and occurs in only 1% of the general population. Genetic testing for BRCA mutation is recommended if a person without cancer has a family member with a known BRCA mutation, or is a patient with breast cancer who develops cancer before age 45 or has a triple negative breast cancer at age 60 or younger, or has a breast cancer at age 50 or younger with personal history of prior breast cancer or ovarian cancer, or has breast cancer at age 50 or younger with a relative with breast cancer, or breast cancer at any age and a relative with breast cancer at age 50 or younger or a male relative with breast cancer.  Men with prostate cancer should be tested if they have a relative with ovary cancer, pancreatic cancer, prostate cancer, or breast cancer at her before age 50.

Women with BRCA mutations have a lifetime risk of:

  • Breast cancer ranging from 50-85%.
  • Ovarian cancer 15-50% for

Men with BRCA2 mutation have a 20% risk of prostate cancer.  They should not undergo prostate screening before age 50.

Men with BRCA1 mutation have a 1-2% risk of breast cancer

Men with BRCA2 mutations have a 6% risk of breast cancer.


Lynch syndrome is also referred to as hereditary non-polyposis colorectal cancer (HNPCC).  Therefore, gene abnormalities that create this syndrome. Patients with Lynch syndrome are particularly predisposed to colon cancer.  Stomach cancer, pancreatic cancer, small bowel cancer, bile duct cancer, and kidney or urinary tract cancers are also increased in Lynch syndrome patients.  Women with Lynch syndrome mutations have a strong increased risk of uterine (endometrial) cancer and ovarian cancer. Up to 5% of colon and rectal cancer cases are thought to be related to Lynch syndrome, and up to 3% of endometrial cancer cases from the uterus are thought to be caused by Lynch syndrome mutations.

Lynch syndrome has been described since the early 1960’s.  Is currently thought that up to 1 of every 300 people may carry a Lynch gene mutation.  Colon cancer that occurs in a Lynch syndrome patient has an unusual tendency to develop in the right colon where it may not cause symptoms and therefore can be very advanced and have tremendous spread prior to any suspicion for the cancer.  Advanced disease will decrease the likely hood of successful treatment after the cancer is found. This cancer often occurs much earlier than his expected for colon cancer. Those patients with the Lynch syndrome colon cancer may develop cancer years prior to when screening colonoscopy is usually initiated.  A high percentage of the young man who developed a Lynch syndrome colon cancer will die of their disease because of the failure to find it when it is early. Women with Lynch syndrome often developed uterine cancer at an unusually young age. The uterine cancer may develop long before the colon cancer. Because uterine cancer often bleeds early in its course these patients will have the uterine cancer diagnosed early and very often cured.  This gives opportunity to recognize the Lynch syndrome mutation and provides an opportunity to recommend early and enhanced screening for these women after they have been successfully treated for the uterine cancer. Recognizing women in the family with uterine cancer due to Lynch syndrome also provides an opportunity to do testing and diagnosis younger male siblings who might otherwise have developed a future colon cancer and perhaps a life-threatening disease.

Lynch syndrome should be suspected if colon cancer or uterine cancer is diagnosed before age 50.  Lynch syndrome should also be suspected in a patient who has a history of both colon cancer and other types of cancer associated with Lynch syndrome.  The patient without cancer should be considered for testing if one or more first-degree relatives had to Lynch syndrome cancers with 1 of those cancers developing before age 50.  Cancer tissue can also be tested for the presence of DNA repair gene function and if those proteins are not represented there is a great likelihood that the patient has a Lynch syndrome mutation.  All uterine cancer patients are now usually tested for these mismatch repair genes. That testing is much cheaper than genetic testing and is used as a screening test, but when abnormal needs to be further evaluated with true genetic testing.  Lynch syndrome genes include MLH1, MSH2, MSH6, PMS2, and EPCAM. Each gene has a different likelihood of creating a cancer.

Colon cancer will occur in 20-80% of patients with Lynch syndrome.

Uterine (endometrial) cancer occurs in up to 60% of Lynch syndrome patients.

Ovarian cancer occurs in up to 38% of Lynch syndrome patients.

Urinary tract cancers occur in up to 18% of Lynch syndrome patients.

Pancreatic cancer occurs in up to 6% of patients with Lynch syndrome.

Dr. Martin is a strong proponent of enhanced screening for cancer screening and of risk reducing surgery for patients with Lynch syndrome mutation.

Patients with known Lynch syndrome mutation may benefit from annual pelvic ultrasound and biopsy of the uterine cavity.  Women who are done having children should consider prophylactic removal of the uterus and ovaries to remove the risk of ovarian cancer or uterine cancer.

Knoxville Gynecologic Cancer Specialists
10810 Parkside Drive, Suite 200
Knoxville, TN 37934
Phone: 865-413-1867
Fax: (865) 218-6001
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