Research recommendations toward a better understanding of the causes of childhood leukemia

The reported increasing incidence rates seen for B-cell precursor ALL (but not for T-ALL or acute myelogenous leukemia (AML)) in industrialized countries 4 point toward a role for the modern lifestyle. However, to date, epidemiological studies have failed to confirm any associations with lifestyle exposures such as smoking, alcohol, diet, social status, and so on. Indeed, to date, the only recognized risk factors for ALL are heavy birth weight 5 , 6 and gender, with boys more often affected than girls (approximate ratio 1.2:1).— However, the validity of these annual increases in industrialized countries is questionable. Are the observed increases partially due to improvements in cancer registration and disease detection and classification? What is the base line incidence world wide or, in other words, how large is the contribution of potentially avoidable environmental factors to the disease? Why are boys more likely to develop ALL? So far, epidemiological studies could not correlate various potential risk factors with the initial versus subsequent genetic events. A translocation event as the first hit has to be the consequence of a double-strand break that is misrepaired, whereas different risk factors reflecting different mechanisms are supposed to be responsible for the additional cooperating genetic changes.— What does the age at onset of leukemia tell us? B-cell precursor ALL has a distinct age peak between 2–5 years of age, except for the subtype characterized by mixed lineage leukemia (MLL) rearrangements that occurs mainly below 1 year. What are the patterns of incidence of ALL and AML in developing countries — is there evidence of a peak between 2–5 years as seen in developed countries?