The etiology of ALL is not known, and although several studies have tried to identify risk factors for leukemic development, definite conclusions cannot be drawn. However, some associations, such as genetic, parental, socioeconomic, and environmental factors, must be considered.

1)Genetic Factors:
Reports have identified families with multiple members affected by leukemia. When an identical twin is diagnosed with ALL, the other twin has a significantly higher risk of developing leukemia; as many as 20% of them will be diagnosed with the disease within 1 year, but the risk is age dependent, decreasing from nearly 100% for the twins when the index case is diagnosed before the age of 1 year to a risk no different from that in other siblings when diagnosed after the age of 4 years. Siblings of patients with leukemia have a fourfold higher risk of developing leukemia than the general population.

Several genetic syndromes have also been associated with leukemia, with the best characterized being Down's syndrome, which accounts for nearly 2% of all ALL cases in children. Other syndromes, such as Bloom syndrome, ataxia telangiectasia, Wiskott-Aldrich syndrome, and Fanconi's anemia, are also associated with an increased risk of leukemia.

2)Parental and Socioeconomic Factors:
Maternal reproductive history is also important. Children of mothers older than 35 years of age may have an increased risk of leukemia, only partially explained by the increased risk of having Down's syndrome. A history of prior fetal loss, especially if there have been multiple miscarriages, has been identified as a risk factor for the offspring. The association of increased weight at birth and childhood ALL has been reported consistently. Parental occupational exposure to such agents as pesticides and benzene may increase the risk of leukemia in offspring, but most of these cases have been acute myelogenous leukemia (AML). There may also be a higher risk for children with a better socioeconomic status, but this is not universally accepted.

3)Environmental Factors:
Exposure to radiation is associated with a definite risk of ALL. In utero exposure increases the risk of ALL over that of control populations. Exposure to low-dose radiation, such as that used in diagnostic radiology, has not been proven to be leukemogenic, but exposure to high doses (like those used in radiotherapy) may be. People exposed to radiation during the atomic disasters at Hiroshima and Nagasaki, as well as people involved in other nuclear exposures, may have as much as a 10- to 20-fold higher risk of developing leukemia.

Exposure to different chemicals has also been associated with an increased risk of leukemia. The best characterized association involves benzene, although more than two thirds of these cases are AML. The exposure to electromagnetic fields has been repeatedly linked to an increased risk of ALL, but the evidence is inconclusive.

Several studies have suggested clustering of cases of childhood leukemia. This clustering usually represents a group of cases occurring within a population, whose incidence is higher than that expected for the general population. This clustering of cases has been attributed to the proximity of environmental hazards, such as nuclear plants. However, evidence of this exposure is lacking in most cases. This and other epidemiologic data, such as the increased incidence of common ALL with higher socioeconomic status and isolation, have led to the hypothesis of an infectious etiology for common ALL in children. According to this hypothesis, common ALL at childhood peak ages might arise after unusual patterns of exposure to common infectious agents. In more developed societies with better hygiene and fewer social contacts early in infancy, common infections are frequently delayed beyond the first year of life and until a higher level of social contacts is made.