Is Diffuse Large B-Cell Lymphoma Inherited? Genetics and 8 Other Risk Factors | MyLymphomaTeam

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Is Diffuse Large B-Cell Lymphoma Inherited? Genetics and 8 Other Risk Factors

Medically reviewed by Leonora Valdez, M.D.
Updated on March 25, 2024

  • There are many risk factors, both inherited and environmental, believed to increase one’s risk of developing diffuse large B-cell lymphoma (DLBCL).
  • Your risk of developing DLBCL rises if you have a parent or sibling who’s had lymphoma or leukemia.
  • 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 DLBCL, you may have concerns about whether this type of lymphoma can be passed down in families. Although a family history of blood cancers does raise the risk of developing DLBCL, it isn’t the only risk factor. DLBCL is usually caused by acquired mutations — DNA changes that develop during a person’s lifetime — related to environmental factors.

Here’s what research shows about family history and the risk of developing DLBCL, along with other risk factors. If you’re worried about developing lymphoma, there are symptoms to watch for that may indicate DLBCL or another type of lymphoma. Always discuss your health concerns with your doctor.

Family History and DLBCL

DLBCL is a fast-growing type of non-Hodgkin lymphoma (NHL). Although a family history in a first-degree blood relative (a parent or a sibling) is considered a risk factor for developing DLBCL, medical researchers don’t fully understand the connection between family history and DLBCL.

One large 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 types of B-cell lymphomas that can progress to DLBCL.

Oncology researchers also looked at more than 121,000 participants in the California Teachers Study and found about a 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 increases in family members outside first-degree relatives.

Despite the association of family history with DLBCL, some hematology research indicates that the distinction between hereditary factors and shared environments in families isn’t clear. In other words, families may share exposure to other risk factors because they live together. For that reason, DLBCL isn’t described as a hereditary disease, although inherited genetic characteristics may cause first-degree blood relatives of people with lymphoma to be likely to develop DLBCL.

Genetic Changes in DLBCL

The genetic changes — also known as mutations or aberrations — 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, commonly occurring in BCL6, BCL2, and MYC genes.
  • Abnormal somatic hypermutation — B cells can go through many gene changes that affect how they produce antibodies, which are important for our immune system.

These genetic alterations make it harder for the body to remove faulty cells. The mutations also make it harder for cells to repair damaged DNA, leading to more mutations and raising the risk that white blood cells will develop into cancer cells. B cells, also known as B lymphocytes, are a type of white blood cell and part of the immune system.

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.

8 Other DLBCL Risk Factors

Family history isn’t the only important risk factor for DLBCL. For example, age, other health conditions, and environmental factors (caused by outside exposures) — or a combination — can also play a role. Any substance or situation associated with more acquired mutations can make it more likely that cancer may develop.

Other important risk factors for DLBCL include age, autoimmune diseases, infections, and exposure to chemotherapy or chemicals such as benzene.

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1. Age

The likelihood of having more acquired 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.

2. Autoimmune Conditions

A combination of genetic and environmental factors leads to autoimmune conditions, in which the immune system attacks your body’s tissues or organs. An overactive immune system means that more immune cells — and possibly more abnormal cells — will be produced.

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.

3. 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. Viruses that have been linked to DLBCL include:

  • Human herpesvirus 8
  • Chronic hepatitis C
  • Hepatitis B
  • Human immunodeficiency virus (HIV)
  • Epstein-Barr virus (EBV)

Some research has shown that EBV may have genetic features that promote inflammation and immune dysfunction linked to the development of lupus and DLBCL in particular.

4. Organ Transplants

People who have had organ transplants have a risk of developing DLBCL more than 12 times higher than the general public. The highest risk was found to be among people who underwent organ transplants at a younger age and those who had lung, pancreas, or kidney-pancreas transplants.

5. Personal History of Cancer

People who have had cancer in the past have a higher risk of developing DLBCL. Research has shown that more than 10 percent of people with a personal history of cancer, especially stomach cancer, develop DLBCL.

6. Chemical Exposure

Environmental exposure to chemicals such as benzene (used in industry), insecticides or pesticides, or certain chemotherapy drugs may increase the risk of NHL. Pesticide exposure has also been linked to poorer response to treatment in people with DLBCL.

Radiation exposure from treating other cancers is also connected to the development of NHL subtypes, including DLBCL.

7. Cigarette Smoking

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

8. Obesity

People with high weight or obesity are also at risk of developing DLBCL. Some research from Seminars in Hematology has indicated that almost 25 percent of DLBCL cases may be linked to obesity.

Screening for DLBCL

Currently, there is no recommended screening exam for NHL. So far, no tests have proven to lower the chance of dying from cancer. If your parent or sibling has had 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.

If you have a family history of NHL, it’s a good idea to discuss risk factors with your doctor and be able to recognize potential lymphoma symptoms.

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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 17,000 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.

Updated on March 25, 2024
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Leonora Valdez, M.D. received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute. 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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