Q: Which cancers can be detected through genetic testing?
A positive test result may cause some people to feel stress, anxiety, anger or even guilt. It also may raise ethical issues, because the information may be relevant to biological relatives and, in some cases, individuals may not want to disclose this information.
People who are considering testing could consult genetic counselors who have specialized education and training in medical genetics. Genetic counselors can provide support during the process, review test results and communicate them to other members of a health-care team.
What is genetic testing?
Our genes are composed of DNA, and variants or changes in DNA can cause genetic mutations. Genetic testing done on a blood or a saliva sample can identify mutations that are linked to an increased risk of certain cancers.
Who should pursue genetic testing for cancer?
Two groups of people could consider genetic testing:
- Individuals who have been diagnosed or have close relatives who have been diagnosed with cancer such as uterine, breast or colorectal cancers at a young age (often younger than 50). Genetic testing would inform decisions about other cancer-screening practices and treatment.
- People at an increased risk of cancer because of family history — a first-degree relative with a genetic mutation, or two or more relatives on the same side of the family with a cancer diagnosis, such as uterine, breast or colorectal cancer — or ancestry such as Ashkenazi Jewish ancestry (from Central Europe or Eastern Europe). People with this ancestry are at an increased risk of mutations in genes called BRCA1 and BRCA2, which are risk factors for some cancers. Ashkenazi Jewish women have a 1-in-40 chance of carrying a BRCA mutation.
Both groups should review their family history in-depth with their health-care team to determine whether genetic testing should be pursued.
Genetic testing for breast, ovarian cancers
The majority of breast and ovarian cancers are nonhereditary, but 5 to 10 percent of such cancers may be caused by inherited mutations in the BRCA1 or BRCA2 genes, or less commonly, other genetic mutations.
If a person has a strong family history of these cancers, such as several close relatives with breast cancer, a male relative with breast cancer, any relatives with ovarian cancer, or if close family members were diagnosed with cancer younger than 50, a physician may recommend testing for the BRCA1 and BRCA2 genes. If there is a family member with a cancer diagnosis, the affected family member could get tested first.
Genetic testing also should be pursued if a person has a diagnosis of triple-negative breast cancer (a type of breast cancer that does not express the estrogen receptor, progesterone receptor or HER2/neu protein).
Breast cancer is less commonly diagnosed in men, and all men with this diagnosis should consider BRCA testing.
When genetic testing shows a mutation in the BRCA1 or BRCA2 genes, a person can take steps that may help detect cancer early, or lower the risk for developing cancer.
Starting at age 25, women with BRCA mutations are advised to undergo a breast-screening MRI annually, in addition to a yearly mammogram, according to the National Comprehensive Cancer Network guidelines. Male BRCA carriers, starting at age 35, should perform self-exams and undergo a clinical breast exam every 12 months with a physician.
Some people may also choose to proceed with breast tissue removal, with a surgery called a prophylactic mastectomy.
In some cases, physicians recommend Tamoxifen to lower the risk of breast cancer.
To lower the risk of ovarian cancer, a woman may choose to have her ovaries removed — by ages 35 to 40 for women with a BRCA1 variant, and by ages 40 to 45 for women with a BRCA2 variant, or “at an age based on earliest age of ovarian cancer diagnosed in the family,” according to the National Comprehensive Cancer Network guidelines.
Genetic testing for colorectal cancer
As many as 1 in 3 people diagnosed with colorectal cancer have other family members with the disease, according to the American Cancer Society. The most common cause of inherited colorectal cancer is called Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer.
Lynch syndrome is caused by a germ line mutation in one of the DNA mismatch repair genes such as MLH1, MSH2, MSH6, PMS2, or a deletion in the EPCAM gene. Genetic testing can detect the mutations that cause Lynch syndrome.
People with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer and other malignancies, such as cancer of the ovary, stomach, small intestine or renal pelvis/ureter.
Lynch syndrome accounts for 2 to 4 percent of all colorectal cancer cases, and approximately 8 percent of colorectal cancer cases diagnosed in people younger than 50.
Lynch syndrome could be the cause:
- If a person gets more than one primary colorectal cancer diagnosis in a short period of time (such as a new colon cancer diagnosis six months after a previous diagnosis).
- If there is a diagnosis of early-onset colorectal cancer or endometrial cancer (before age 50).
- If there are multiple Lynch-associated cancers diagnosed in a person.
- If there are a number of family members diagnosed with Lynch-associated cancers.
People diagnosed with Lynch syndrome can take steps to discover cancer early. They should get a colonoscopy every one or two years, starting between the ages of 20 and 25, or 2 to 5 years before the earliest age of diagnosis of colorectal cancer in the family.
There may be additional cancer-screening recommendations depending on the genetic mutation identified and a person’s family history.
Amy Comander is a breast oncologist and director of Breast Oncology and Survivorship at the Massachusetts General Hospital Cancer Center in Waltham and at Newton-Wellesley Hospital, and medical director, and director of Lifestyle Medicine, at the cancer center. Comander also is an instructor at Harvard Medical School.