Is Diffuse Large B-Cell Lymphoma Hereditary? | MyLymphomaTeam

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Is Diffuse Large B-Cell Lymphoma Hereditary?

Medically reviewed by Prakruthi Jaladhar, M.D., DNB
Posted on June 23, 2023

  • Your risk of developing diffuse large B-cell lymphoma (DLBCL) rises if you have a parent or sibling who’s had lymphoma or leukemia.
  • Researchers don’t yet have a clear understanding about which inherited genes influence the risk of DLBCL.
  • Other factors affect DLBCL risk, including age, autoimmune conditions, certain viral infections, and environmental factors.

If you or a loved one has been diagnosed with diffuse large B-cell lymphoma, you may have concerns about whether this type of lymphoma can be passed down in families. While a family history of blood cancers does raise the risk of developing DLBCL, inheritance isn’t the only risk factor. DLBCL is usually caused by acquired mutations — changes that develop in one person — related to environmental factors.

This article will cover what research shows about family history and the risk of DLBCL, other risk factors, and symptoms to watch for if you’re worried about developing lymphoma.

Family History and DLBCL

DLBCL, a fast-growing type of non-Hodgkin lymphoma (NHL), can run in families through inherited gene mutations — genetic changes passed from parent to child. Although most people with DLBCL won’t pass it on to their children, family history in a first-degree blood relative (a parent or a sibling) does increase this risk. Several studies in the past 20 years have explored this connection.

One large 2015 review of studies found that people with a first-degree relative with NHL were about 1.8 times more likely to develop DLBCL. There was also an increased risk of NHL in people who had a first-degree relative with Hodgkin lymphoma or leukemia. DLBCL risk was 2.1 times higher in people with a family history of Hodgkin lymphoma, who also had slightly raised risks of follicular lymphoma and chronic lymphocytic leukemia (CLL). Follicular lymphoma and CLL are slower-growing NHL subgroups that can progress to DLBCL.

Researchers also looked at more than 121,000 participants in the California Teachers Study and found about 1.7 times increase in the risk of DLBCL in people who had a first-degree relative with lymphoma.

Based on data from disease registries, the risk of DLBCL is higher if a first-degree relative has DLBCL. Studies have found that these people were nearly 10 times more likely to develop this cancer, according to the 2015 review. So far, there’s no evidence that the risk of NHL or DLBCL goes up in family members outside first-degree relatives.

Genetic Changes in DLBCL

The genetic changes that lead to DLBCL have been well studied. Damaged genes can lead to DLBCL in two ways:

  • Chromosomal translocation — Part of a chromosome breaks off and attaches to a different chromosome.
  • Abnormal somatic hypermutation — B cells develop many mutations in the genes that help make immune proteins called antibodies.

These mutations can inhibit apoptosis (cell death), making it harder for the body to remove cancer cells. The mutations also hamper DNA repair, leading to further mutations and, perhaps, problems with the BCL6 gene. BCL6 contains the information needed to make a protein important for white blood cell development. Lymphoma is a cancer of B cells, white blood cells that produce antibodies.

More than 150 gene changes that can lead to DLBCL have been identified through genome sequencing — testing that looks at all the DNA in a cell. More clinical trials are needed to understand which gene mutations run in families. Hopefully, future knowledge of DLBCL genetics will help identify genes that can pass from parents to offspring.

Other DLBCL Risk Factors

Family history isn’t the only important risk factor for DLBCL. For example, age, other conditions, and environmental factors (caused by outside exposures) — or a combination of these — can also play a role. Another term for acquired mutations that develop as a result of environmental factors is “de novo.”

Age

The likelihood of having more gene mutations increases with age, so the risk of being diagnosed with lymphoma is greater as you get older. The prognosis (outlook) for DLBCL diagnosed later in life is also worse. Most people are over 60 when they’re diagnosed.

Autoimmune Conditions

A combination of genetic and environmental factors leads to autoimmune conditions, in which the immune system attacks your body’s own tissues. An overactive immune system means that more immune cells — and possibly more abnormal cells — will be produced. This process increases the risk of DLBCL because this blood cancer is caused by abnormal B lymphocytes, a type of immune cell.

Autoimmune conditions that may increase the risk of NHL and DLBCL include:

  • Celiac disease
  • Lupus
  • Rheumatoid arthritis
  • Sjögren’s syndrome

However, most people who have an autoimmune disease will not develop lymphoma.

Infections

Certain infections are environmental risk factors for lymphoma. Although most infections don’t cause chronic problems, some are associated with an increased risk of cancer. Certain viruses, including Epstein-Barr virus and human herpes virus 8, may prompt white blood cells to turn into cancer cells. Chronic hepatitis C infection has also been linked to DLBCL — but again, most people with these infections won’t develop lymphoma.

Chemical Exposure

Environmental exposure to chemicals, such as benzene (used in industry), insecticides, or chemotherapy drugs may increase the risk of NHL. Radiation exposure from treating other cancers is also connected to the development of NHL subtypes, including DLBCL.

Cigarette Smoking

Smoking cigarettes, especially over many years, increases risk of developing lymphomas in general. People who smoke have about a 1.02 times higher risk of developing DLBCL than people who don’t smoke.

Screening for DLBCL

Currently, there is no recommended screening exam for NHL, because no available tests have shown that these tests can lower the chance of dying from cancer. That said, if your parent or sibling has DLBCL or another NHL subtype, you should review your family history with a doctor. Be sure to also ask about any other factors that may affect your risk.

Everyone should look out for symptoms of lymphoma, but this awareness is especially important if you have a parent or sibling with the disease. Common early symptoms of lymphoma include:

  • Swollen lymph nodes in the neck, armpit, or groin
  • Fever, chills, or night sweats
  • Unintended weight loss
  • Swollen belly
  • Tiredness

If you’ve been diagnosed with and treated for DLBCL, it’s also important to watch for these symptoms as possible signs of relapse. Talk to your doctor if you’re worried you may be relapsing. Your health care team is there to help you along every step of your journey with lymphoma.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. More than 14,000 members understand what it’s like to face lymphoma and can provide support and answers.

Are you living with DLBCL? Do you have family members with the condition? Have you discussed inherited risks with your family or with your doctor? Share your experience or post a comment on your Activities page to start a conversation.

Posted on June 23, 2023
All updates must be accompanied by text or a picture.

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Prakruthi Jaladhar, M.D., DNB completed her medical education at Mysore Medical College, followed by an internal medicine residency at Kempegowda Institute of Medical Sciences (KIMS) in Bangalore. Learn more about her here
Chelsea Alvarado, M.D. earned her Bachelor of Science in biochemistry from Temple University in Philadelphia, Pennsylvania, and her Doctor of Medicine from the University of Maryland School of Medicine in Baltimore, Maryland. Learn more about her here

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