What are the risk factors for non-Hodgkin lymphoma in children?

A risk factor is anything that might affect a person’s chance of getting cancer. Different cancers have different risk factors. Some cancer risk factors, like smoking, can be controlled. Others, like a person's age or family history, can't be changed.

But risk factors don’t tell us everything. Having a risk factor, or even many risk factors, does not mean that you will get the disease. And many people who get the disease may have few or no known risk factors. Even if a person has a risk factor and develops cancer, it is often very hard to know how much that risk factor may have contributed to the cancer.

Lifestyle-related risk factors such as body weight, physical activity, diet, and tobacco use play a major role in many adult cancers. But these factors usually take many years to influence cancer risk, and they are not thought to have much of an effect on the risk of childhood cancers, including non-Hodgkin lymphomas.

Most children with non-Hodgkin lymphoma do not have any known risk factors for this disease that can be changed. But researchers have found some factors that may put children at increased risk.

Age, gender, and race

Non-Hodgkin lymphoma is rare in children in general, but it is more common in older children than in younger ones. It is also more common in boys than in girls and in white children than in black children.

Weakened immune systems

Some types of immune system problems have been linked with a higher risk of non-Hodgkin lymphoma in children.

Congenital (present at birth) immune deficiency syndromes

Some genetic (inherited) syndromes can cause children to be born with an abnormal immune system. Along with an increased risk of serious infections, these children also have a higher risk of developing non-Hodgkin lymphoma (and sometimes other cancers as well). These syndromes include:

• Wiskott-Aldrich syndrome
• Severe combined immunodeficiency syndrome (SCID)
• Ataxia-telangiectasia
• Common variable immunodeficiency
• Bloom syndrome
• X-linked lymphoproliferative syndrome

Organ transplants

Children who have received organ transplants are treated with drugs that weaken their immune system to prevent it from attacking the new organs. These children have an increased risk of developing non-Hodgkin lymphoma that is almost always caused by Epstein-Barr virus infection (see below). The risk depends on which drugs and what doses are used.

HIV/AIDS

Infection with human immunodeficiency virus (HIV), also known as the AIDS virus, is a cause of immune system deficiency in children and adults. Children with HIV generally get the infection from contact with their mother's blood, usually before or during birth. HIV infection is a risk factor for developing non-Hodgkin lymphoma, so doctors may recommend that children with non-Hodgkin lymphoma be tested for HIV infection.

Radiation exposure

Radiation exposure may be a minor risk factor in childhood non-Hodgkin lymphoma.

Survivors of atomic bombs and nuclear reactor accidents have an increased risk of developing some types of cancer. Leukemia and thyroid cancers are the most common, but there is a slightly increased risk of non-Hodgkin lymphoma as well.

Patients treated with radiation therapy for other cancers have a slightly increased risk of developing non-Hodgkin lymphoma later in life. However, it usually takes many years for this to happen, so these secondary cases of non-Hodgkin lymphoma are more common in adults than children.

Epstein-Barr virus infection

In areas of Africa where Burkitt lymphoma is common, chronic infection with both malaria and the Epstein-Barr virus (EBV) is an important risk factor. EBV has been linked with as many as 90% of Burkitt lymphomas in Africa. In the United States, EBV has been linked with about 15% of Burkitt lymphomas.

EBV infection is life-long, although in most people it doesn’t cause serious problems. In Americans who are first infected with EBV as teens or young adults, it can cause infectious mononucleosis, sometimes known simply as mono. Most Americans have been infected with EBV by the time they are adults, but the infection seems to occur later in life in the United States than in Africa, which may help explain why it is less likely to cause lymphoma here. Another factor may be that in certain parts of Africa, children’s immune systems also have to deal with other infections, such as malaria, which, together with EBV, may cause the body to make more lymphocytes.

Exactly how EBV is linked to Burkitt lymphoma is not completely understood, but it seems to have to do with the ability of the virus to infect and alter B lymphocytes. (For more information, see the section, “Do we know what causes non-Hodgkin lymphoma in children?”)

It is important to note that most children with non-Hodgkin lymphoma do not have known risk factors that can be changed. There is nothing these children or their parents could have done to prevent this cancer.

Other possible risk factors

Some research has suggested that a family history of non-Hodgkin lymphoma (in a brother, sister, or parent) might raise the risk of lymphoma. Lymphoma risk may also be higher in children of older mothers. More research is needed to confirm these findings, but the increased risk, if any, is likely to be small overall.