Folic acid food fortification is associated with a decline in neuroblastoma.
BACKGROUND
Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known.


METHODS
We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification.


RESULTS
An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89).


CONCLUSIONS
Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.
French
Amy E
AE
Motherrisk Program and Division of Hematology and Oncology, The Hospital for Sick Children, and Department of Medicine and Prehospital Care Programme, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Ontario, Canada.
Grant
Ron
R
Weitzman
Sheila
S
Ray
Joel G
JG
Vermeulen
Marian J
MJ
Sung
Lillian
L
Greenberg
Mark
M
Koren
Gideon
G
D002170:Canada / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D005492:Folic Acid / Q000494:pharmacology*; D005527:Food, Fortified; D018197:Hepatoblastoma / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology; D009447:Neuroblastoma / Q000453:epidemiology* / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology; D012189:Retrospective Studies
D005492:Folic Acid