Most childhood leukemia has no single identifiable cause. Scientists have found genetic and environmental factors that raise the risk, but the majority of children who develop leukemia have none of these known risk factors. Equally important: nothing a parent or child did caused the disease. Childhood leukemia appears to result from a combination of genetic vulnerability and environmental triggers, often beginning with DNA changes that happen before a child is even born.
How Childhood Leukemia Starts
Leukemia begins when a single white blood cell in the bone marrow acquires a DNA mutation that causes it to multiply uncontrollably. In children, this typically follows a “two-hit” pattern. The first genetic change often occurs in the womb, creating a small population of abnormal cells. These cells aren’t yet cancerous. A second mutation, happening months or years after birth, can push those cells into full leukemia.
Studies of identical twins have provided some of the clearest evidence for this two-step process. When one twin develops leukemia in infancy, the other almost always does too, because the first mutation arose in one twin and spread to the other through their shared blood supply in the womb. But the second mutation is different in each twin, confirming it happens independently after birth. This means a child can carry pre-leukemic cells from birth and never develop the disease if that second hit doesn’t occur.
Acute lymphoblastic leukemia (ALL), the most common type, peaks between ages 2 and 5. Acute myeloid leukemia (AML), the second most common, is more likely in the first year of life and again during the teenage years. These age patterns offer clues about when the critical mutations tend to strike.
The Role of Genetics and Inherited Conditions
Only a small fraction of childhood leukemia cases are linked to inherited DNA changes passed from parent to child. Most of the mutations that cause leukemia are acquired randomly during cell division, not inherited. Still, certain genetic conditions do raise the risk substantially.
Children with Down syndrome face roughly a 10- to 20-fold increased risk of leukemia compared to the general pediatric population, with an overall lifetime childhood risk of about 2% to 3%. They can develop both ALL and AML, and a significant number experience a temporary condition called transient abnormal myelopoiesis in infancy, where abnormal blood cells appear but often resolve on their own before sometimes progressing to leukemia.
Other inherited conditions that increase risk include Li-Fraumeni syndrome, neurofibromatosis type 1, and Noonan syndrome. Bone marrow failure syndromes like Fanconi anemia and Shwachman-Diamond syndrome also predispose children to leukemia, as do immune deficiency conditions like ataxia-telangiectasia and Bloom syndrome. These are all rare, and collectively they account for only a small percentage of childhood leukemia cases.
Having a sibling with leukemia raises a child’s risk slightly, but the overall chance remains low. Family history is not a major driver for most cases.
The “Delayed Infection” Theory
One of the most compelling explanations for the most common childhood leukemia, ALL, comes from decades of research by Mel Greaves at the Institute of Cancer Research in London. His theory suggests that ALL is, paradoxically, a disease of modern cleanliness.
The idea works like this: a child’s immune system needs to be “primed” by exposure to common microbes during the first year of life. Children who grow up in very clean environments, with limited contact with other infants or older children, may miss this early training. When these children later encounter common infections (ordinary viruses and bacteria), their immune systems can overreact in a way that triggers the second genetic hit needed to turn pre-leukemic cells into full-blown leukemia.
Several lines of evidence support this theory. Population studies have found that early daycare attendance and breastfeeding, both of which expose infants to microbes sooner, appear to protect against ALL. In animal experiments, researchers engineered mice carrying a leukemia-initiating gene and raised them in ultra-clean, germ-free conditions. When those mice were moved into an environment with common microbes, they developed ALL. Mice raised with normal microbial exposure from the start did not.
This doesn’t mean infections cause leukemia. Rather, it suggests that the timing of infection matters. Early microbial exposure helps the immune system develop normally, while delayed exposure in a child who already carries a pre-leukemic mutation can be the trigger that tips the balance.
Radiation Exposure
Exposure to high levels of ionizing radiation is one of the more clearly established environmental risk factors for childhood leukemia. The strongest evidence comes from studies of children exposed to nuclear fallout and from medical imaging research.
A detailed analysis of studies on prenatal radiation exposure found that a dose as low as 10 millisieverts to an embryo or fetus during pregnancy causes a measurable increase in childhood cancer risk. For context, a single CT scan of the abdomen delivers roughly 8 to 10 millisieverts. Even lower doses, around 1.5 millisieverts from nuclear fallout, have been associated with a small increase in leukemia risk among children under 5.
The good news is that routine, low-level exposures like a single diagnostic X-ray carry very small absolute risk. The concern is primarily with repeated or high-dose exposures. Modern medical imaging protocols for children are specifically designed to minimize radiation doses for this reason.
Chemical Exposures Before and After Birth
Benzene, a chemical found in gasoline, industrial solvents, and some paints, is one of the most studied chemical risk factors. A national Swiss cohort study found that children whose mothers were occupationally exposed to benzene during pregnancy had roughly double the risk of developing ALL, with the strongest association in children under age 5. A 2016 meta-analysis found that maternal benzene exposure carried a higher risk than paternal exposure, suggesting that direct fetal exposure during pregnancy is the more likely pathway. The plausible explanation is that benzene can damage DNA in the developing child’s blood cells while still in the womb.
Pesticides are another area of concern. A meta-analysis published by the American Academy of Pediatrics found that children exposed to indoor residential insecticides had a 47% increased risk of leukemia compared to unexposed children. Notably, outdoor pesticide use did not carry the same risk, likely because indoor exposure results in higher and more sustained contact with the chemicals. Emerging research has also flagged PFAS (sometimes called “forever chemicals”) and air pollution as potential contributors, though the evidence is still developing for those exposures.
Children who have previously been treated with certain chemotherapy drugs for another cancer also face an elevated risk of developing leukemia later. This is a known trade-off of cancer treatment, not a cause that applies to the general population.
Immune System Suppression
Children who take medications to suppress their immune systems, most commonly after organ transplants, have a higher risk of developing ALL and lymphoma. The suppressed immune system is less able to detect and destroy abnormal cells before they multiply. This risk factor applies to a very specific group of children and is carefully monitored by transplant teams.
What Parents Should Take Away
The vast majority of childhood leukemia cases cannot be traced to a single preventable cause. The disease typically results from a chain of unlucky genetic events, most of which begin before birth and are influenced by factors no parent can control. Known risk factors like inherited syndromes, radiation, and chemical exposures account for only a small share of cases. The “delayed infection” theory offers a promising framework for understanding ALL, and it suggests that normal early childhood microbial exposure, through breastfeeding, social contact with other children, and ordinary play, may help the immune system develop in ways that reduce risk.