Follicular lymphoma is a type of non-Hodgkin lymphoma (NHL). Scientists have found that most people with any type of lymphoma don’t have a family history of the condition. Instead, the genetic mutations (variations) associated with lymphoma are thought to be acquired (picked up) throughout your life from sources such as radiation, chemicals, and infections.

Scientists have found that most people with lymphoma don’t have a family history of the condition.

However, cancer research shows that first-degree relatives of people with follicular lymphoma have a higher risk of also developing the disease. This suggests that some risk factors for follicular lymphoma may be passed down in families. In this article, we’ll talk about the causes of follicular lymphoma and the evidence that some genes may be passed down in families.

What Causes Follicular Lymphoma?

Researchers don’t fully understand what causes some people to develop follicular lymphoma. They think it occurs due to a mix of environmental, immune-related, and genetic risk factors.

Environmental Factors

Environmental factors associated with follicular lymphoma include:

• Exposure to toxins like benzene or pesticides
• History of certain infections
• Smoking or secondhand smoke

Immune System-Related Factors

Follicular lymphoma is a cancer that causes B cells (a type of lymphocyte, or white blood cell) to grow uncontrollably. B cells are specialized immune cells that make antibodies (immune proteins) that help identify and kill invading germs.

Because follicular lymphoma is a cancer of immune-related cells, it makes sense that changes to your immune system may play a role in its development. Immune system changes associated with lymphoma include:

• Weakened immune systems
• Autoimmune diseases (when the immune system mistakenly attacks your own body tissues)
• Chronic (long-term) infections

Genetic Factors

Genetic mutations associated with follicular lymphoma are usually acquired during a person’s lifetime. Follicular lymphoma is most commonly diagnosed in older adults. Half of people diagnosed with follicular lymphoma are older than 65. The older you are, the more risk you have of acquiring a genetic mutation associated with follicular lymphoma.

What’s the Evidence That Some Risk Factors for Follicular Lymphoma May Be Inherited?

One of the strongest indications that risk factors for follicular lymphoma may be inherited (passed down) is the fact that cases of this lymphoma often occur within families. Studies show that first-degree relatives (parents, siblings, or children) of someone with follicular lymphoma are about four times more likely to develop the disease compared to the general population. Additionally, having a family history of chronic lymphocytic leukemia — another type of blood cancer — can also increase the risk of follicular lymphoma.

Researchers are still working to identify specific genes that may be passed down and contribute to the development of follicular lymphoma.

First-degree relatives (parents, siblings, or children) of someone with follicular lymphoma are about four times more likely to develop the disease, compared to the general population.

Which Genes Are Involved in Follicular Lymphoma?

Your genes are the blueprint your cells use to grow and divide properly. A mutation in any of the genes related to cell growth can cause cells to grow uncontrollably. The genetic variants that cause cancer can be inherited from your parents or acquired during your life. So far, researchers have found a few genes associated with follicular lymphoma.

BCL2

BCL2 is a gene that contains the instructions for making a protein that stops apoptosis. Apoptosis is the normal process of cell death. Certain acquired genetic issues can lead to BCL2 overexpression. This means the BCL2 makes too much protein. This overproduction prevents apoptosis. So, the cells with this issue don’t die the way they’re supposed to. They can then grow out of control.

In follicular lymphoma, abnormalities in the BCL2 gene are caused by a translocation — a specific gene rearrangement. A translocation happens when parts of chromosomes (the structures that contain your genetic material) break off and swap places. In most cases of follicular lymphoma, a translocation occurs between chromosomes 14 and 18. This results in the overproduction of the BCL2 gene.

About 85 percent of people with follicular lymphoma have this BCL2 translocation. Some people, however, develop follicular lymphoma without this genetic mutation. This finding suggests that other genetic factors must also play a role in the development of the disease.

EZH2

About 1 in 4 people with follicular lymphoma have a mutation found in the EZH2 gene. Changes in this gene are associated with uncontrolled cell growth. Like the BCL2 translocation, EZH2 mutations are considered an acquired mutation.

MAP2K1

Mutations in the MAP2K1 gene are linked to pediatric follicular lymphoma. Most children with follicular lymphoma don’t have the BCL2 translocation found in adults. Instead, MAP2K1 mutations drive rapid cell growth. This mutation is also considered an acquired mutation.

TNFRSF14

Mutations in the TNFRSF14 gene are common in children and young adults with follicular lymphoma. The TNFRSF14 gene codes for a tumor suppressor protein that normally helps control cell growth. When this gene is mutated or deleted, it can lead to uncontrolled cell growth.

Other Genes

Researchers are continuing to discover additional genes that may play a role in follicular lymphoma. Genome-wide association (GWA) studies, which scan the entire genome of large groups of people, have identified several genes that may be linked to the disease. Some of these genes are related to human leukocyte antigens (HLAs), which help the immune system distinguish between the body’s own cells and foreign invaders.

Talk to Your Health Care Provider About Genetic Mutations Related to Follicular Lymphoma

Genetic testing can help people understand their risk for some types of cancer. However, there are currently no specific genetic tests available for follicular lymphoma.

At this time, health experts don’t recommend genetic testing for family members of people with follicular lymphoma. While first-degree relatives (parents, siblings, and children) have a four-fold increased risk of developing follicular lymphoma, the overall risk is still very low. You may qualify for a clinical trial studying genetic mutations in families with a history of follicular lymphoma. Ask your health care provider for more information.

Currently, health experts don’t recommend that family members be tested for genetic risk factors related to follicular lymphoma.

Your care team can help you understand symptoms of follicular lymphoma to watch for and ways to lower your risk.

Follicular Lymphoma Symptoms To Watch For

You should be aware of the symptoms of follicular lymphoma if you have a family member diagnosed with the condition. Common symptoms include:

• Swollen lymph nodes, especially in the neck, armpit, or groin
• Fatigue or weakness
• Fever that doesn’t go away
• Unintended weight loss
• Night sweats

If you experience any of these symptoms, talk to your health care provider right away.

Lowering Your Risk of Follicular Lymphoma

While there is no way to completely prevent follicular lymphoma, especially when inherited factors are involved, there are steps you can take to help lower your overall risk of lymphoma. These include:

• Taking steps to prevent infections linked to lymphoma, such as HIV and human T-cell lymphotropic virus (HTLV-1)
• Maintaining a healthy weight
• Staying physically active
• Eating a well-balanced diet rich in fruits, vegetables, and whole grains

Talk to Others Who Understand

On MyLymphomaTeam, the social network for people with lymphoma and their loved ones, more than 19,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

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