Dataset Information

Childhood cancer incidence trends in association with US folic acid fortification (1986-2008).

ABSTRACT:

Objective

Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996-1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification.

Methods

Using Surveillance, Epidemiology, and End Results program data (1986-2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models.

Results

From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns.

Conclusions

These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification.

SUBMITTER: Linabery AM

PROVIDER: S-EPMC3362910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Study question: Do short-term and long-term exposures to low dose folic acid supplementation alter DNA methylation in sperm? Summary answer: No alterations in sperm DNA methylation patterns were found following the administration of low dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. What is known already: Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate’s role in one carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high dose (5 mg/day) folic acid supplementation. Participants/materials, setting, methods: Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array. Main results and the role of chance: Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre- and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. Limitations, reasons for caution: This study was limited to the number of participants available in each cohort, in particular those who were not exposed to early (pre-1998) fortification of food with folic acid. While genome-wide DNA methylation was assessed with several techniques that targeted genic and CpG rich regions, intergenic regions were less well interrogated. Wider implications of the findings: Overall, our findings provide evidence that short term exposure to low dose folic acid supplements of 400 μg/day, over a period of 3 months, a duration of time that might occur during infertility treatments, has no major impact on the sperm DNA methylome.