Abstract 629: Childhood cancer incidence trends in association with folic acid fortification in the United States (1986-2008)
Authors: Linabery Amy M. , Johnson Kimberly J. , Ross Julie A. 
Published: August 2012

Abstract
Folic acid plays a critical role in embryonic development and sufficient maternal prenatal folic acid consumption significantly reduces the incidence of congenital abnormalities in offspring. Epidemiological evidence supports the hypothesis that maternal prenatal folic acid supplementation lowers the risk of childhood cancer in offspring; however a systematic evaluation of population-based childhood cancer incidence trends following fortification of enriched grain products with folic acid in the U.S. in 1996-1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with U.S. folic acid fortification. Using Surveillance, Epidemiology, and End Results program data (1986-2008) we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs) to compare pre- and post-fortification incidence rates in children aged 0-4 years. Using joinpoint and loess regression models, we looked for inflection points during this period where the incidence trend changed in magnitude and/or direction. From 1986-2008, 8,829 children aged 0-4 years were diagnosed with malignancies, including 3,790 and 3,299 in utero during the pre- and post-fortification periods, respectively. Pre- and post-fortification incidence rates were similar for all cancers combined (IRR=1.01, 95% CI: 0.96-1.06) and for most specific cancer types examined. Rates of ependymomas (IRR=0.70, 95% CI: 0.51-0.97), primitive neuroectodermal tumors (PNETs) (IRR=0.56, 95% CI: 0.37-0.84) and Wilms tumor (WT) (IRR=0.80, 95% CI: 0.68-0.95) were significantly lower post-fortification. Notably, a greater reduction in post-fortification incidence was observed for the latter two subtypes upon restricting the analysis to infants, in whom any true effect of folic acid is expected to be greater. Joinpoint regression models detected increasing PNET incidence from 1986-1993 (annual percent change, APC=11.5, 95% CI: -5.0-31.0) followed by a sharp decrease from 1993-2008 (APC=−7.4%, 95% CI: -12.1- -2.4), and increasing WT incidence from 1986-1997 (APC=2.2, 95% CI: -1.2-5.8) followed by a sizable decline from 1997-2008 (APC=−4.0%, 95% CI: -7.3- -0.6). Loess curves indicated similar patterns. These results provide support for decreases in PNET and WT incidence, but not other childhood cancers, following U.S. folic acid fortification. Ten years of data are now available post-fortification and any substantial changes in childhood cancer rates attributable to fortification should be evident. Drawing firm conclusions regarding the isolated effects of folic acid is difficult, however, as other temporal trends occurred during the time period examined. Alternative study designs are required to rule out other explanations and confirm causal relationships. Supported by NIH Grants T32 CA099936 and K05 CA157439, and Children's Cancer Research Fund, Minneapolis, MN. A.M. Linabery and K.J. Johnson contributed equally to this work.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 629. doi:1538-7445.AM2012-629