Your genetics influence many aspects of your health, including your risk of lymphoma. Certain inherited conditions are associated with a higher cancer risk. These conditions can influence how fast cells grow and divide or how effectively your immune system fights cancer. Inherited genetic mutations (changes) play a major role in about 5 percent to 10 percent of all cancers, including lymphoma.

In this article, we’ll explore several genetic disorders that may raise the risk of lymphoma. We’ll also look at how other health conditions contribute to this risk. To learn more about your lymphoma risk, talk to your healthcare provider.

Is Lymphoma Hereditary?

Lymphoma isn’t a cancer that’s directly inherited from a parent or other family member. However, if lymphoma runs in your family, it can raise your risk. Having a family history of lymphoma means you’re more likely to develop it yourself. Researchers believe this is because family members share small genetic changes (variants) that may be linked with lymphoma.

Your lymphoma risk depends on the specific type of lymphoma. For example, people with first-degree relatives (parents, siblings, or children) who’ve had non-Hodgkin lymphoma (NHL) are at a higher risk. Some types of NHL, like follicular lymphoma, are more strongly linked to inherited gene changes.

Although most cases of Hodgkin lymphoma don’t involve a hereditary factor, having a sibling with the disease increases your risk. Identical twins have the highest risk because they share the same genetics.

About Genetic Mutations and Lymphoma

There are two primary types of genetic mutations — germline (inherited) and somatic (acquired). Inherited genetic mutations are passed down from parents to their children. These genetic changes are present in almost every cell in a person’s body.

Acquired gene mutations occur throughout our lives, especially as we age. These changes happen when DNA — the genetic material inside our cells — becomes damaged. Acquired mutations can be caused by environmental factors, including:

• Certain viral infections, such as Epstein-Barr virus (EBV)
• Radiation exposure
• Toxins or pollution in the environment
• The natural aging process

Acquired mutations can also happen at random. As cells divide and make copies of themselves, errors may occur. Uncorrected errors can lead to mutations that affect how cells function, potentially increasing the risk of cancer.

Most cancers, including lymphoma, are caused by acquired mutations rather than inherited ones.

Why Do Some Genetic Mutations Increase the Risk of Lymphoma?

Scientists don’t yet fully understand why some people with genetic risk factors develop lymphoma and others don’t. Ongoing research continues to explore how specific genetic changes influence lymphoma risk. It’s important to remember that a risk factor isn’t the same as a cause — just because you have certain risk factors doesn’t mean you’ll develop lymphoma.

Inflammation and Immune System Functioning

Like many lymphomas, autoimmune diseases are thought to be the result of both genetic and environmental factors. Studies show that lymphoma and autoimmune diseases may share common genetic factors. For instance, researchers have found that many of the gene changes linked to Hodgkin lymphoma are also involved in rheumatoid arthritis (RA) and multiple sclerosis.

People with Sjögren’s disease are significantly more likely to develop NHL. RA has been linked to diffuse large B-cell lymphoma (DLBCL), and systemic lupus erythematosus is associated with a four- to sevenfold increased risk of lymphoma.

Some medications used to treat autoimmune diseases may also increase the risk of NHL, although researchers need to learn more about this connection. Chronic inflammation from autoimmune diseases can damage healthy tissues. In the case of lymphoma, this creates an environment that may help cancer cells grow and divide.

Specific Genes or Gene Functions Are Affected

Certain genes — and specific parts of genes — help control how cells grow, divide, and repair themselves. When these genes are altered or mutated, the balance of cell growth and repair can be disrupted, increasing the risk of cancer.

You may be familiar with BRCA1 and BRCA2, genes known for their role in the risk of breast cancer and ovarian cancer. Normally, these genes act like brakes on a car, helping to slow cell growth. They also repair damaged DNA.

Researchers recently found that BRCA1 and BRCA2 germline variants are also linked to other types of cancer, including lymphoma. In one study of almost 2,000 people with lymphoma, those with BRCA1 mutations were nearly six times more likely to develop lymphoma compared to those without the gene change. A BRCA2 mutation almost tripled the risk of lymphoma.

BRCA2 mutations may also affect the risk of NHL in children and teens. One study found that BRCA2 mutations raised lymphoma risk fivefold in this group. Most of the participants with NHL also had a family history of BRCA2-related cancers.

Germline Mutations That Increase Lymphoma Risk

Some inherited genetic disorders and gene mutations are linked to an increased risk of certain types of lymphoma. If you have a personal or family history of an inherited condition, your doctor may recommend genetic testing to help determine if you have a predisposition to lymphoma.

Disorders That Weaken the Immune System

Your immune system works hard to identify and destroy cancerous cells before they grow and spread. A weakened immune system may not function as effectively, which can raise the risk of NHL.

Wiskott-Aldrich Syndrome

Wiskott-Aldrich syndrome is a rare genetic disease that affects specialized immune cells called lymphocytes — a type of white blood cell that helps protect the body from infection. This condition raises the risk of blood cancers such as lymphoma and leukemia. People with Wiskott-Aldrich syndrome are also more likely to develop autoimmune disorders such as RA. The American Cancer Society notes that autoimmune diseases are linked with increased lymphoma risk.

Ataxia-Telangiectasia

Another inherited disorder, ataxia-telangiectasia, affects both the nervous and immune systems. Ataxia-telangiectasia is caused by changes in the ATM gene, which helps repair damaged DNA and control cell growth. Studies show that people with ATM mutations are about 2.6 times as likely to develop lymphoma compared to people who don’t have these genetic changes.

Klinefelter Syndrome

Klinefelter syndrome is a genetic condition in which males are born with one or more extra X chromosomes, according to MedlinePlus. Doctors and researchers debate the association between this condition and lymphoma. Studies show that men with Klinefelter syndrome are at an increased risk of developing solid tumors, according to the journal Pediatric Endocrinology Reviews: PER. However, only a few small case reports have explored this connection, and more research is needed.

Li-Fraumeni Syndrome and Li-Fraumeni-Like Syndrome

Li-Fraumeni syndrome and Li-Fraumeni-like syndrome are rare genetic disorders that increase the risk of several types of cancer, including lymphomas. People with this syndrome often have a mutation in the TP53 gene, which plays a critical role in controlling cell growth and repairing damaged DNA. About 90 percent of people with Li-Fraumeni syndrome develop cancer by age 69.

Nijmegen Breakage Syndrome

Nijmegen breakage syndrome is a rare inherited condition caused by changes in the NBN gene, which makes a protein called nibrin. This protein helps repair DNA damage caused by environmental toxins or radiation exposure. Without healthy nibrin proteins, DNA breaks build up in cells, which can turn cancerous.

People with Nijmegen breakage syndrome have a significantly increased risk of NHL. According to MedlinePlus, around 50 percent of people with this syndrome will develop NHL, often during childhood or early adolescence (before age 15).

Work With Your Healthcare Team

Understanding your family history and genetic background can help you make informed decisions about your health. If you have concerns about your lymphoma risk, talk to your doctor or a genetic counselor. Staying informed is one of the best ways to take charge of your well-being.

Find Your Team

On MyLymphomaTeam, the social network for people with lymphoma and their loved ones, more than 21,000 people come together to ask questions, give advice, and share their stories with others who understand life with follicular lymphoma.

Do you have a genetic disorder that raises your risk of lymphoma? How has this shaped your cancer journey and treatment plan? Share your experience in the comments below, or start a conversation by posting on your Activities page.