What Do Genes Have to Do With Cancer?

Within every cell in your body, there are genes that provide instructions to the cells, particularly on how to grow and divide. Occasionally, these genes can be abnormal or mutated, which can lead your cells to grow out of control. The uncontrolled growth of abnormal cells is what leads to cancer.

What is Genetic Testing?

It can sometimes seem like cancer just runs in your family. For the most part, when multiple people in one family have cancer, it’s due to chance or a collective exposure to a common risk factor, like smoking. Occasionally though, cancer can be caused by an abnormal gene that has been passed down from your parents, their parents, and further generations back. Only 5-10% of all cancer diagnoses are the result of inherited gene mutations.

Genetic testing is a way to see if your body has any of the gene abnormalities that are linked to cancer.

What Genes Can Be Found Through Testing?

There are a bunch of different gene mutations that have been linked to cancer. Most gene mutations are rare, but common genetic mutations include:

Hereditary Breast and Ovarian Cancer (HBOC) Syndrome

You’ve probably heard of BRCA1 and BRCA2, which are inherited gene mutations that cause HBOC. If you test positive for HBOC, you are at increased risk of breast and ovarian cancers.

Lynch Syndrome (aka Hereditary Non-Polyposis Colorectal Cancer)

Lynch Syndrome is caused by a mutation in the MLH1, MSH2, MSH6, PMS1, and/or PMS2 genes. If you have Lynch Syndrome, you are at increased risk of developing colorectal, endometrial, ovarian, stomach, small intestine, pancreatic, kidney, brain, uretural, and bile duct cancers.

Li-Fraumeni Syndrome

Li-Fraumeni Syndrome is caused by inherited mutations in the TP53 gene. If you test positive for Li-Fraumeni Syndrome, you are at increased risk of sarcoma (such as osteossarcoma and soft-tissue sarcomas), leukemia, brain cancer, cancer of the adrenal cortex, and breast cancer.

Familial Adenomatous Polyposis (FAP)

FAP causes hundreds of polyps in the colon and rectum. Over time, this can result in an increased risk of colorectal cancer.

Who Should Complete Genetic Testing?

If you’re interested in genetic testing, start by thinking about your family’s cancer history. For each cancer diagnosis in your family, think about:

• Who has the cancer diagnosis?
• What is their relation to you, including which side of the family they’re on?
• What type of cancer is it?
• How old were they when they were first diagnosed?
• Did they ever get a second cancer diagnosis?
• Did they have known risk factors for their cancer (i.e. smoking for lung cancer)?

After you’ve considered your overall family history of cancer, if you’re interested in genetic testing for a specific type of gene mutation, learn more below.

Testing for Hereditary Breast and Ovarian Cancer (HBOC) Syndrome

BRCA1 and/or BRCA2 mutations

If you decide to get genetic testing for BRCA1 and/or BRCA2, you’re looking to see if you have inherited these gene mutations that can increase your risk for breast and ovarian cancers. However, it’s important to understand that the vast majority of breast and ovarian cancers are not caused by inherited mutations like BRCA1 and BRCA2, so genetic testing will not provide any helpful information. In fact, only about 3% of all breast and 10% of all ovarian cancer diagnoses are caused by BRCA1 or BRCA2.

In general, genetic testing for BRCA1 and/or BRCA2 is recommended if you have:

• A strong family history of breast and/or ovarian cancer
• A moderate family history of breast and/or ovarian cancer and are of Ashkenazi Jewish or Eastern European ancestry
• A personal history of breast cancer and have other risk factors
• A personal history of ovarian, fallopian tube, or primary peritoneal cancer
• A known BRCA1, BRCA2, or other inherited mutation in your family

Ideally, the first person who undergoes genetic testing in your family should be someone who has or had breast or ovarian cancer. If no one in your family who has had cancer is able to be tested, an unaffected family member can be tested, but the results may not be as informative.

Testing for Lynch Syndrome

MLH1, MSH2, MSH6, PMS1, and/or PMS2 mutations

If you decide to get genetic testing for MLH1, MSH2, MSH6, PMS1, and/or PMS2, you’re looking to see if you have inherited these gene mutations that can increase your risk for colorectal, endometrial, ovarian, stomach, small intestine, pancreatic, kidney, brain, uretural, and bile duct cancers.

When deciding whether you’re a good fit for this type of genetic counseling or testing, your doctor will use one of two sets of guidelines: the Amsterdam criteria (based on family history) and the Bethesda guidelines (for people diagnosed with colorectal cancer).

The Amsterdam Criteria

Research has shown that many people who have inherited Lynch syndrome and the associated gene mutations from their families have similar characteristics. These characteristics make up the Amsterdam criteria:

• You have at least three relatives that have a cancer diagnosis that is linked with Lynch Syndrome AND:
  • One of them is a first-degree relative (parent, sibling, or child) to the other two relatives.
  • At least two successive generations are affected with Lynch Syndrome.
  • At least one relative had their cancer when they were younger than 50 years old.

You may want to undergo genetic counseling if those criteria apply to your family. However, just because your family satisfied the Amsterdam criteria doesn’t always mean you have Lynch Syndrome.

The Bethesda Guidelines

The Bethesda guidelines are used to decide whether a person with colorectal cancer should be tested for Lynch Syndrome. The Bethesda criteria includes at least one of the following:

• You were younger than 50 years old when diagnosed with colorectal cancer.
• You have or had a second colorectal cancer or another cancer (endometrial, stomach, pancreas, small intestine, ovary, kidney, brain, ureters, or bile duct) linked to Lynch syndrome.
• You are younger than 60 years old and the cancer has certain characteristics of Lynch syndrome.
• You have a first-degree relative (parent, sibling, or child) younger than 50 who was diagnosed with colorectal cancer or another cancer linked to Lynch syndrome.
• You have two or more first- or second-degree relatives (aunts, uncles, nieces, nephews, or grandparents) who had colorectal cancer or another Lynch syndrome-related cancer.

If you have or had colorectal cancer and have any of the Bethesda criteria, genetic testing may be appropriate for you.

Testing for Li-Fraumeni Syndrome

TP53 mutation

If you decide to get genetic testing for Li-Fraumeni Syndrome, you’re looking to see if you have inherited a TP53 gene mutation that can increase your risk for sarcoma (such as osteossarcoma and soft-tissue sarcomas), leukemia, brain cancer, cancer of the adrenal cortex, and breast cancer.

When deciding whether you’re a good fit for this type of genetic counseling or testing, your doctor will use this criteria:

• You have a sarcoma before age 45.
• Your parents, siblings, or children were diagnosed with any cancer before age 45.
• Your grandparents, aunts, uncles, nieces, nephews, or grandchildren were diagnosed with any cancer before age 45.

If you have Li-Fraumeni syndrome and were assigned female at birth, you have a nearly 100% chance of developing breast cancer. Overall, having a Li-Fraumeni syndrome diagnosis results in a 90% chance of developing one or more cancers in your lifetime and a 50% chance of developing cancer before age 30.

Testing for Familial Adenomatous Polyposis (FAP)

If you decide to get genetic testing for FAP, you’re looking to see if you have inherited a gene mutation that can increase your risk for colorectal cancer. If you have close relatives (parents, siblings, and children) that have been diagnosed with FAP, you should be tested for the genetic mutation.

You may be a good fit for this type of genetic counseling or testing if you have close family members who have been diagnosed with FAP or you are experiencing symptoms of FAP, including:

• A large amount of polyps in your colon and rectum, usually starting by your mid-teens
• Osteomas (non-cancerous bony growths), usually found on the jaw
• Extra, missing, or unerupted teeth
• An eye condition called congenital hypertrophy of the retinal pigment epithelium (CHRPE)
• Non-cancerous skin changes including epidermoid cysts and fibromas
• Adrenal masses

If you are a parent and have FAP yourself, it is important to have your child tested at a young age for the inherited mutation. FAP causes polyps to develop at a young age, which can over time lead to colorectal cancer. Having FAP results in a nearly 100% lifetime risk of developing colorectal cancer, usually before age 50.

What’s the Recommendation?

Genetic testing isn’t perfect and can bring up a lot of unanticipated feelings, regardless of your results. It’s important to start by talking to your doctor about genetic testing, then you should meet with a genetic counselor to discuss your options, and finally you can undergo genetic testing if it is appropriate for you.

Genetic Counseling

Depending on your personal or family health history, your doctor may refer you for genetic counseling. Genetic counselors will talk you through the process and the pros and cons of genetic testing. They can provide you with information, resources, and support for you and your family. After your counseling session, you will decide whether or not genetic testing is appropriate for you. Depending on your overall risk, the cost of genetic counseling is often covered by insurance.

Genetic Testing (if appropriate)

If you decide to undergo genetic testing, a sample of your blood, hair, cheek cells, urine, amniotic fluid, or other body tissues will be taken to be examined in a lab. After the results are back, a genetic counselor will help you understand the meaning of your test results.

What Do My Results Mean?

After you undergo genetic testing, a genetic counselor will review your results with you to help you understand what they mean. Here are some things to keep in mind…

After BRCA1 and/or BRCA2 Testing

The results of genetic testing for BRCA1 and/or BRCA2 can come back as:

• Positive for the mutation(s) tested for – This means that the test did find a BRCA1 and/or BRCA2 mutation in your cells. Even with a positive result, there is no guarantee you will develop breast cancer. You can also take steps to lower your risk of breast cancer (and other cancers) by making healthy lifestyle choices. If you’ve already been diagnosed with breast cancer when you test positive for a BRCA1 and/or BRCA2 mutation, your treatment options may change.
• Negative for the mutation(s) tested for – This means that the test did not find a BRCA1 and/or BRCA2 mutation in your cells. Just because you test negative, though, doesn’t mean you’re not still at risk for cancer. You can always take steps to lower your risk of breast cancer (and other cancers) by making healthy lifestyle choices.
• Inconclusive – This means that the test wasn’t able to tell for sure if you have a BRCA1 and/or BRCA2 gene mutation.
• Positive for a variant of unknown significance (VUS) – This means that the test did find a gene change, but it’s not known yet whether this particular change affects your cancer risk.

After Lynch Syndrome Testing

If you test positive for Lynch Syndrome (or if members of your family have tested positive), you should start colonoscopy screening during your early 20s or 2-5 years younger than the youngest family member with a diagnosis (whichever is earlier). You should be screened every 1-2 years to make sure any new polyps are found and removed before they can become cancerous.

After Li-Fraumeni Syndrome Testing

If you test positive for Li-Fraumeni Syndrome, you have an increased risk of developing cancer, including more than one type of cancer at the same time. You should remain vigilant for any signs of cancer, avoid activities that can increase your cancer risk, and complete recommended cancer screenings to catch cancer early when it’s easiest to treat.

Children with Li-Fraumeni Syndrome may need to complete these cancer screenings:

• Annual physical exam including a close check of skin health and neurological function
• Periodic blood tests, including a complete blood count (CBC)
• Tests for hormone-producing cancers starting in the adrenal glands
• Annual MRIs of the brain and body
• Periodic ultrasound of the abdomen

Adults with Li-Fraumeni Syndrome may need to complete the cancer screenings listed above, as well as:

• A colonoscopy every 2-5 years starting in the early 20s
• Women should get a breast exam performed by a doctor every 6 months, plus a mammogram and breast MRI at least once a year starting in the early 20s

After FAP Testing

If you test positive for FAP, you should start colonoscopy screening at 10 to 15 years old. You’ll likely also need to have your colon removed when you are in your 20s to prevent cancer from developing.

Source: American Cancer Society; Centers for Disease Control and Prevention; Cleveland Clinic; National Cancer Institute