What Causes Chronic Lymphocytic Leukemia (CLL)?.

Scientists aren’t exactly sure what causes the genetic mutations that result in CLL. Exposure to certain chemicals and family history may increase your risk.

Leukemia is a type of cancer that affects your blood cells and the cells involved in producing those blood cells. Chronic lymphocytic leukemia (CLL) affects your lymphocytes — white blood cells that help your body fight off infections.

It’s not exactly known what causes CLL. Several factors may be involved in causing CLL, including your genetics and family history, as well as your exposure to certain chemicals in your environment.

Read on to learn more about the suspected causes of CLL, whether CLL can run in families, and other possible risk factors for CLL to keep in mind.

How genetic changes cause CLL

All cancers result from a genetic change that causes changes in your cells. These genetic changes (mutations) could be inherited, develop from environmental factors (like smoking or chemicals), or occur randomly.

It’s unclear what causes the genetic mutations that cause CLL, but scientists have identified several genes that may be involved. Most cases result from a deletion, which is when part of a chromosome is lost, but other types of mutations can also cause CLL.

A 2017 review explains how mutations in chromosomes 11, 12, 13, or 17 can affect your likelihood of developing CLL:

• deletion of 13q14, which can affect regular cell death (apoptosis) of your lymphocytes
• deletion of 11q22-23, which is connected to a more aggressive form of CLL that’s harder to treat
• deletion of 17p12, which is associated with resistance to common treatments like rituximab (Rituxan) and chemotherapy
• trisomy 12, which happens when you have three copies of chromosome 12 instead of two

These mutations in chromosomes can help predict diagnosis and treatment outcomes.

You can have one or more of these mutations. The mutations may also cause other conditions. For example, trisomy 12 can also cause other physical and cognitive effects, such as heart defects and developmental delays.

Other genetic biomarkers linked to CLL include:

• disruption to the TP53 gene, which helps prevent tumors from growing
• mutations in IGHV, which can increase resistance to treatments like chemoimmunotherapy (CIT)

Exposure to chemicals and CLL

Exposure to certain chemicals may also increase your risk of developing CLL.

Exposure to Agent Orange is a well-documented risk factor for developing CLL. Agent Orange is an herbicide that was commonly used during the Vietnam War to disrupt agricultural food production across the country.

A 2018 study of over 2,000 Vietnam veterans found that exposure to Agent Orange:

• resulted in diagnosis with CLL at a younger age than is typical (around 63 years old instead of 70)
• is associated with a longer overall survival rate than people with CLL who weren’t exposed, especially among those with 11q deletion
• was more effectively treated with fludarabine, chlorambucil (Leukeran), and rituximab

Some studies have linked other pesticides to CLL, but more research is needed to confirm this link.

A 2017 study also links radon in the home to increased rates of CLL, but again, more research is needed.

Does CLL run in families?

Although gene mutations are responsible for CLL, most cases don’t result from mutations passed down through families.

Still, there’s strong evidence suggesting that you may be more likely to develop CLL if someone in your immediate family has also been diagnosed with CLL:

• People born to those with CLL are more likely to be diagnosed 20 years younger than their parents were.
• People with siblings or parents with CLL are twice as likely to be diagnosed.
• People with close relatives with CLL are more likely to have a condition called monoclonal B-cell lymphocytosis, another risk factor for CLL.

Other risk factors for CLL

People who live in North America and Europe appear to be more likely to develop CLL than people who live in Asia.

Other risk factors that may affect your likelihood of developing CLL include:

• Age: CLL is more commonly diagnosed in people over 50 years old and rarely in anyone younger than 40.
• Sex: People assigned male at birth are more likely to develop CLL than people assigned female at birth.
• Monoclonal B-cell lymphocytosis: This condition causes your body to produce more lymphocytes than is typical. This can increase your risk of developing CLL.

Frequently asked questions

What is the most common cause of CLL?

The most common causes of CLL are genetic mutations in chromosomes or specific genes.

Some of these can be passed down from your parents, but they can also happen because of spontaneous gene mutations during your lifetime.

Can I prevent CLL?

There’s no surefire way to prevent CLL, but reducing your exposure to environmental factors may help lower your risk of developing it.

How quickly does CLL develop?

CLL usually doesn’t develop very quickly. It can take 2–20 years before symptoms become noticeable.

Takeaway

CLL is a rare type of blood cancer that results from genetic mutations that affect your lymphocytes. Scientists have identified specific mutations that cause CLL, but what causes them is still unclear. Exposure to environmental toxins like Agent Orange is one risk factor.

There’s no way to prevent CLL. But knowing your risk factors can help you learn how to reduce your risk and improve your long-term outlook.