Epidemiology of childhood leukemia: a targeted overview.

Despite the challenges involved in studying the epidemiology of a rare disease, the last two decades have provided considerable information regarding the probable causes of childhood leukemia, in which current evidence suggests an important role for genetic susceptibility and external factors originating from the environment. The genome-wide association study approach has led to the identification of several associated genes, thereby confirming the polygenic nature of childhood leukemia. Ongoing studies have shown that many of these loci, which were originally identified in populations of European ancestry, are also important in the Japanese population. Regarding potential external exposures, increasing evidence is becoming available to elucidate the role of infectious agents and the influence of immune maturation in early life. Epidemiological evidence supports the prevailing hypotheses related to the effect of population mixing on transient increases in the childhood leukemia rates, as well as the role of delayed exposures to common infections in propagating an aberrant immune response and subsequent leukemia risk. Future advances in the investigation of childhood leukemia and other rare diseases along with coordinated studies and collaborations are needed, owing to stringent sample size requirements to support statistically robust comparisons and opportunities for independent validation.