What Are the Risk Factors for Childhood Leukemia?

A risk factor is anything that increases your chance of getting a disease such as cancer. Risk factors can be classified as inherited (genetic), lifestyle-related, or environmental. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, larynx, bladder, kidney, and several other organs. But having a risk factor, or even several, does not mean that you will get the disease.


Lifestyle-related Risk Factors

Lifestyle-related risk factors for some cancers include an unhealthy diet, harmful habits such as smoking and excessive drinking of alcoholic beverages, and excessive sun exposure.

In general, lifestyle-related factors are the most significant influence contributing to cancers in adults, but are the least important part of childhood cancer risk.

There is some suggestion that drinking a lot of alcohol during pregnancy may increase the risk of acute myelogenous leukemia (AML) in the child.

Genetic Risk Factors

Certain genetic (inherited) diseases cause children to be born with an abnormal or deficient immune system. In addition to developing serious infections due to reduced immune defenses, these children also have an increased risk of developing leukemia. (Although these immune deficiency diseases can be passed on to children, adult leukemia survivors who do not have these inherited diseases do not pass an increased risk of leukemia on to their children.)

There are also several other inherited disorders that increase a child’s risk of developing leukemia:

• Li-Fraumeni syndrome – This is a rare condition that increases a person's risk of developing leukemia, bone or soft tissue sarcomas, breast cancer, and brain tumors.
  
• Down syndrome (trisomy 21) – Children with this disorder have an increased risk of developing leukemia. Instead of having two copies of each of the 23 chromosomes, children with Down syndrome have 3 copies (1 more than usual) of chromosome 21. In ways that are not completely understood, this extra chromosome 21 causes mental retardation and a characteristic facial appearance. Children with Down syndrome are 15 times more likely to develop either acute lymphocytic leukemia (ALL) or AML than are other children. Down syndrome is also associated with transient leukemia – a leukemia-like condition within the first month of life, which resolves on its own without the use of chemotherapy.
  
• Klinefelter syndrome – This is a genetic condition in which males have an extra "x" chromosome. This causes infertility, prevents normal development of male features (such as body hair, deep voice, etc.) and is also associated with an increased risk of developing leukemia.

Several other genetic disorders (neurofibromatosis, ataxia telangectasia, Wiscott-Aldrich Syndrome, and Fanconi anemia) also carry an increased risk of developing leukemia, but these disorders more commonly lead to non-Hodgkin lymphoma and other types of cancers.

A Twin With Leukemia

The sibling (brother or sister) of an identical twin who develops ALL or AML before 6 years of age has a 20% to 25% chance of developing leukemia. Doctors think that this occurs because of a genetic change during fetal life that is shared by both fetuses. Fraternal (not identical) twins and other brothers and sisters have slightly increased chances (2 to 4 times normal) of developing leukemia.

Environmental Risk Factors

Environmental risk factors are influences, such as radiation and certain chemicals, in our surroundings that increase the likelihood of developing diseases such as leukemias.

Radiation exposure: Radiation injury is a major environmental risk factor in developing childhood leukemia. Japanese survivors of the atomic bomb had a 20-fold increased risk of developing AML, usually within 6 to 8 years after exposure. Similar risks occurred after exposure to radiation from nuclear reactor accidents. Exposure of the fetus to significant radiation within the first months of development may also carry up to a 5-fold increased risk of developing ALL.

Radiation therapy and chemotherapy: Children and adults treated for other cancers with radiation therapy and chemotherapy have a higher risk of developing a second cancer, usually AML, later in life. Treatment with certain chemotherapy drugs such as alkylating agents (a class that includes cyclophosphamide and chlorambucil) and epipodophyllotoxins (such as etoposide and teniposide) is associated with a higher risk of a second malignancy such as leukemia. These leukemias usually develop within 5 to 10 years of treatment and tend to be difficult to treat.

Immune system suppression: Patients who are receiving intensive therapy to suppress their immune function (mainly organ transplant patients) have an increased risk of developing cancer, especially of the lymphoid system. This includes ALL.

Certain chemicals: Exposure to chemicals such as benzene may cause AML in adults and, rarely, in children. ALL has not been linked to any cancer-causing chemicals.

Other factors that have been studied for a possible association with ALL include exposure to insecticides; mother’s age when child was born; mother’s use of alcohol, cigarettes, diethylstilbestrol (DES), or contraceptives; father’s workplace exposure to chemicals and solvents; and chemical contamination of ground water. None of these factors has been linked conclusively to ALL.