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Abstract
Leukemia is the most common childhood cancer and a major source of morbidity and mortality. The etiology of childhood leukemia remains largely unknown. Cytogenetic abnormalities determine disease subtypes, prognosis, clinical presentation, and course and may help in discovering etiological factors. Epidemiologic investigations of leukemia are complicated by many factors, including the rarity of the disease, necessitating careful study design. Two emerging areas of interest in leukemia etiology are birth weight and diet. High birth weight has been associated with increased risk of childhood leukemia. The biological mechanism behind this association may involve insulin-like growth factor I (IGF-I), which is associated with high birth weight. IGF-I may act by increasing the absolute number of stem cells available for transformation, stimulating the growth of cells that are already transformed, or a combination of effects. Diet has been linked with leukemia. Maternal dietary DNA topoisomerase II (DNAt2) inhibitor intake is associated with infant acute myeloid leukemia (AML) with the MLL gene translocation. Increased intake of fruits and vegetables has been associated with decreased leukemia risk and, relatedly, lack of maternal folate supplementation has been associated with increased childhood leukemia risk, possibly by causing DNA hypomethylation and increased DNA strand breaks. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms modify this risk.
| Abbreviations and Glossary | ||
| ALL | = | acute lymphoblastic leukemia |
| AML | = | acute myeloid leukemia |
| CALLA | = | common ALL antigen |
| CCRN | = | Children's Cancer Research Network |
| CI | = | confidence interval—numbers flanking a measure of association, such as an odds ratio, that describe the role of chance in an observation |
| COG | = | Children's Oncology Group |
| DNAt2 | = | DNA topoisomerase II, an enzyme involved in DNA replication |
| FAB | = | French-American-British |
| FFQ | = | food frequency questionnaire |
| GH | = | growth hormone |
| IGFBP | = | IGF-binding protein |
| IGFR | = | IGF receptor |
| IGF | = | insulin-like growth factors, a family of somatotropins similar in structure to insulin |
| MTHFR | = | methylenetetrahydrofolate reductase, an enzyme involved in folate metabolism |
| NQ01 | = | NAD(P)H: quinone oxidoreductase 1, a multifunctional enzyme whose properties include detoxifying flavonoids |
| OR | = | odds ratio, a measure of association between disease and a putative causal exposure |
| RDD | = | random-digit dialing |
| THF | = | tetrahydrofolate |
| Abbreviations and Glossary | ||
| ALL | = | acute lymphoblastic leukemia |
| AML | = | acute myeloid leukemia |
| CALLA | = | common ALL antigen |
| CCRN | = | Children's Cancer Research Network |
| CI | = | confidence interval—numbers flanking a measure of association, such as an odds ratio, that describe the role of chance in an observation |
| COG | = | Children's Oncology Group |
| DNAt2 | = | DNA topoisomerase II, an enzyme involved in DNA replication |
| FAB | = | French-American-British |
| FFQ | = | food frequency questionnaire |
| GH | = | growth hormone |
| IGFBP | = | IGF-binding protein |
| IGFR | = | IGF receptor |
| IGF | = | insulin-like growth factors, a family of somatotropins similar in structure to insulin |
| MTHFR | = | methylenetetrahydrofolate reductase, an enzyme involved in folate metabolism |
| NQ01 | = | NAD(P)H: quinone oxidoreductase 1, a multifunctional enzyme whose properties include detoxifying flavonoids |
| OR | = | odds ratio, a measure of association between disease and a putative causal exposure |
| RDD | = | random-digit dialing |
| THF | = | tetrahydrofolate |
Notes
*Editor's note: More recent papers than those cited by the authors have documented the relatively poor bioavailability of most flavonoids. They undergo conjugation by intestinal cells prior to or during absorption, lose biological activity, and being water soluble, are rapidly secreted, mainly in the urine. See, for example, Goldberg et al. (Clin Biochem 2003; 36: 79–87) and Kroon et al. (Am J Clin Nutr 2004; 80:15–21).