Genes passed through families seem to contribute to chronic lymphocytic leukemia (CLL) development. Although a family history increases your risk, most people with this history don’t develop CLL.

Chronic lymphocytic leukemia (CLL) is a usually slow-growing type of leukemia that starts in a kind of white blood cell called lymphocytes. Despite being the most common type of leukemia in Western countries, researchers have identified few risk factors for CLL.

A combination of genetic and environmental factors likely contributes to its development. Along with a family history, researchers have identified exposure to some herbicides and pesticides as potential risk factors.

In this article, we examine what we know about the genetics of CLL and other known risk factors.

Language matters

In this article, we use the terms “male” and “female” to refer to someone’s sex assigned at birth. For information about the difference between sex and gender, see this article.

The development of CLL is complex. Researchers know that a combination of inherited genes and environmental factors likely play a role, but for most people with CLL, an underlying cause is never identified.

CLL has one of the strongest family risks of any cancer, but still most people don’t have a family history and most people who do have a family history don’t develop it.

According to the American Cancer Society, inherited mutations are rarely thought to cause CLL. Genetic changes linked to CLL usually occur during your lifetime.

Incidence rates and disease onset

CLL is the most common type of leukemia in Western countries, making up to 30% of cases. People with a relative with CLL have anywhere from two times to 8.5 times higher risk of developing CLL than people without a family history.

Mutations in more than 40 locations have been linked with an increased risk of CLL. Genes mutations in people with CLL frequently occur in:

  • SF3B1
  • NOTCH1
  • ATM
  • TP53

Most people who develop CLL don’t receive a diagnosis until they’re over the age of 50 years. The average age is around 70 years, and it’s very rare in people under 40 years. Some studies have found CLL linked to a family history may develop 10 to 20 years earlier. But other studies have found no difference in the age of onset.

Should you get genetic testing?

There’s currently no evidence that genetic testing benefits people who haven’t already developed signs or symptoms of CLL. Genetic testing can be important during the diagnostic process because some genetic abnormalities might influence your treatment and outlook.

The loss of part of chromosome 13 is usually linked to a better outlook, whereas mutations in chromosomes 11 or 17 are often linked to more aggressive disease.

Environmental factors are also thought to play a role in the development of CLL. But researchers have identified relatively few risk factors.

Increasing age is one of the most established risk factors, and about 90% of cases occur in people over 50 years.

Other possible risk factors include:

  • male sex, as opposed to female sex
  • exposure to certain herbicides and pesticides, such as Agent Orange used during the Vietnam War
  • radon (a heavy radioactive gaseous element) exposure at home
  • living in North America or Europe, compared with Asia

Asian people living in the United States have a comparable risk of CLL with people living in Asia, suggesting that people of Asian heritage may be less genetically prone than people of other ancestries.

According to the American Cancer Society, there’s currently no screening test for CLL because it’s rare, and testing hasn’t been indicated to offer any benefit. CLL may be found on routine blood tests, even if you don’t have any signs or symptoms of the disease.

It’s important to visit a doctor if you develop any signs or symptoms of leukemia for a proper diagnosis. Many conditions other than leukemia can cause these symptoms, but it’s best to get a proper diagnosis to rule out leukemia or other potentially serious problems.

CLL symptoms tend to be general and mimic those of many other conditions. They usually get worse over time, but in the beginning, you may mistake them as symptoms of the flu or other mild illness.

Signs and symptoms include:

It’s a good idea to visit a doctor if you develop any of these symptoms, especially if you have multiple symptoms without another obvious cause.

CLL is sometimes linked to inherited genes passed through families. But most people who receive a diagnosis of CLL don’t have a family history and most people with a family history don’t go on to develop CLL.

Doctors don’t regularly test for CLL due to its rarity and a lack of proven benefit of testing.

It’s important to see a doctor if you suspect you may have CLL or any other type of leukemia.