In most people, chronic lymphocytic leukemia (CLL) is caused by spontaneous mutations (changes) that occur throughout their life. CLL — also referred to as small lymphocytic lymphoma (SLL) — is a slow-growing type of blood cancer. Although there is a slightly increased risk of CLL in people with a family history of the disease, most of them don’t go on to develop it.

In this article, we’ll discuss the genetic causes behind CLL, what risk factors increase the likelihood of developing CLL, and how it can affect people with a family history of the disease. By understanding your family’s risk of CLL, you can take steps to monitor your health.

Gene Mutations in Cancer

Cancer is caused by mutations in your DNA that make your cells grow and divide uncontrollably. To better understand how CLL may be hereditary, it’s important to understand how these gene changes occur.

There are two types of mutations — inherited and acquired. Inherited mutations are passed down through families from parents to their children. These mutations are found in every cell’s DNA from birth, meaning they can continue to be passed on.

Acquired mutations are much more common than inherited mutations. These gene changes happen spontaneously throughout a person’s life, typically as a result of their environment. Exposure to carcinogens (cancer-causing substances) like tobacco smoke, air pollution, chemicals, and radiation can cause acquired mutations. Unlike inherited mutations, acquired mutations are found in only a fraction of cells in the body — this means that they can’t be passed on.

What Causes CLL?

CLL is caused by mutations in your blood stem cells that make lymphocytes, or white blood cells (WBCs). These specialized cells can mature into T cells or B cells that help your immune system fight infections. CLL is a type of B-cell lymphoma that occurs when your body makes too many abnormal B cells (cancer cells or CLL cells) that crowd out the healthy cells in your bone marrow. These CLL cells can’t properly mature, making it harder for your body to fight infections and stay healthy.

Your cells have 23 pairs of chromosomes that make up your DNA, each set coming from your parents. CLL cells typically have one of three mutations, usually a deletion or loss of a piece of DNA from chromosomes 13, 11, or 17. Some people may also have an extra copy of chromosome 12 (known as trisomy 12). These mutations are typically acquired during your lifetime.

As you age, your DNA has a harder time repairing itself after it’s been damaged. Mistakes in this repair process can lead to mutations in your blood stem cells — this is why nearly 90 percent of people who have CLL are typically over the age of 50.

Research shows that exposure to radon in your home and to the herbicide Agent Orange used during the Vietnam War can increase the risk of developing CLL. A handful of studies have also suggested that exposure to pesticides used in farming practices may also be linked to CLL, but more research is needed to confirm these findings.

Can CLL Be Passed Down in Families?

According to the American Cancer Society, CLL is rarely caused by inherited mutations. This means it’s very unlikely that CLL is passed down from parents to their children. Certain gene mutations that can increase the risk of cancer are heritable — however, just because you have one of these mutations doesn’t mean you’ll go on to develop CLL.

A person has a 0.4 percent chance of developing CLL at some point in their lifetime. Studies show that if they have a sibling, parent, or child (first-degree relative) with CLL, their risk increases to 2.15 percent. If a person has two or more first-degree relatives with CLL, their risk increases to almost 9 percent.

One study of more than 16 million people in Sweden found that people with CLL also tend to have a family history of lymphoproliferative disorders — other types of blood cancer that cause uncontrolled production of abnormal blood cells.

CLL, Gene Changes, and Environment

Doctors and researchers haven’t yet found a single gene responsible for CLL development that can be passed down through the family. Instead, they believe having small, single-letter changes or variants in the genome (genetic code) increases the risk of CLL in first-degree relatives. Siblings share around half of their DNA with one another, meaning they may have inherited the same gene variants.

Many first-degree relatives live together in the same environment and may be exposed to the same chemicals, pollution, and other carcinogens. Together, the combination of shared genetics and environment likely contributes to the risk of CLL within families.

While there appears to be an increased risk of developing CLL if you have first-degree relatives who also have the disease, the overall risk is still low. There’s also no guarantee that you or a family member will develop CLL if you share similar gene variants or mutations. If you’re living with CLL and you’re concerned about the specific risk to your family members, your doctor, oncologist, or hematologist can help answer your questions.

Can You Lower Your Risk of CLL?

While you and your family can’t change your DNA to lower your risk of CLL, you can take steps to monitor your health and watch out for the disease. Be sure to let your doctor know about your family history of CLL. It’s also important to go to all of your regular doctors’ appointments and get blood work done as recommended.

Attend Annual Checkups and Watch for Symptoms

Many people with CLL don’t show any symptoms early in the disease — instead, their cancer is caught during routine blood work. An unexplained high WBC count that isn’t caused by an infection is usually the most common finding that points to CLL.

Knowing the signs and symptoms of CLL can also help you or your loved ones seek a diagnosis and treatment sooner rather than later. CLL symptoms usually don’t show themselves until the disease has progressed, and they can include:

• B symptoms — Drenching night sweats, unexplained fever, and unexplained weight loss
• Fatigue
• Anemia (low red blood cell count)
• Shortness of breath
• Lymph node swelling, especially in the neck
• Feeling full after eating little to no food (signs of an enlarged liver or spleen)
• Getting sick or having infections more often, especially in the skin, kidneys, or lungs

Genetic Testing

If you’re interested, you can talk to your doctor or oncologist about genetic testing. They can perform DNA sequencing (a way to look for gene changes) to look for mutations or shared gene variants in you and your family members. This testing is most helpful for determining mutations in people diagnosed with CLL — including mutations in the immunoglobulin heavy chain (IGHV) gene, which can determine the prognosis (outlook) and treatment plan.

Join a Clinical Trial

The National Cancer Institute is currently running a clinical trial to study families with multiple relatives who have CLL. This study is focused on finding gene variants or mutations associated with CLL. Investigators are also looking into identifying biomarkers and profiling certain gene changes or patterns that may help doctors predict family members who are at risk of developing CLL. If you and your family would like to participate in cancer research and help others living with CLL, talk to your doctor about this clinical trial.

CLL has some links to genetics, but it is not commonly passed down from one generation to the next. Certain genetic mutations can raise the chances of developing CLL, but most cases do not have a clear inheritance pattern. Although having a family member with CLL slightly increases the risk, it is important to know that the overall risk remains relatively low. Scientists are still studying how our genes and the environment work together in the development of CLL. If you have concerns about your risk of CLL (or any other health condition), it’s best to talk to a health care professional who can offer information and guidance based on your specific circumstances.

Talk With Others Who Understand

MyLeukemiaTeam is the online social network for people with leukemia and their loved ones. On MyLeukemiaTeam, more than 14,000 members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you or a close family member living with CLL? Do you have more questions for your doctor or oncologist about the heredity of CLL? Share your experiences in the comments below, or start a conversation by posting on your Activities page.