Abstract 2763: Maternal folate intake at periconception and genome-wide DNA methylation modifications at birth in children
| Autor: | Seung-Tae Lee, Joseph L. Wiemels, Amanda W. Singer, E. Andres Houseman, Catherine Metayer, Semira Gonseth, Sébastien Nusslé, Mi Zhou, Ritu Roy, Margaret Wrensch, Adam J. de Smith |
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| Rok vydání: | 2015 |
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| Zdroj: | Cancer Research. 75:2763-2763 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Introduction Folate supplementation during pregnancy was previously associated with a lower risk of acute lymphoblastic childhood leukemia (ALL). Folate is involved in the “one-carbon” metabolic cycle necessary for shuttling methyl groups for DNA methylation. Given the observation that aberrant DNA methylation patterns are a characteristic of leukemic cells during ALL oncogenesis, we hypothesized that (1) low folate exposure during fetal development might modify the neonate's DNA genome-wide methylation pattern, and that (2) such a modified pattern can lead to ALL development. Here we investigate the first part of this hypothesis. Methods We analyzed healthy control participants of the California Childhood Leukemia case-control study. Participants’ peri-conception folate exposure was estimated from self-reported maternal folate intake and supplements, which was derived from a food frequency questionnaire on the diet in the year prior to pregnancy, as a surrogate for nutrient “environment” during the peri-conception period. DNA obtained from archived neonatal blood spots was purified, treated with bisulfite and assayed on the Illumina Infinium 450K genome-wide DNA methylation array. After removing cross-reacting probes, SNP-related and polymorphic CpGs, we analyzed the association of folate with methylation intensity of 319,265 CpGs in two independent datasets (n set 1 = 167 and n set 2 = 176). Models were adjusted for cell mixture, sex, gestational age, and race. We used a false discovery rate with random resampling to reduce the number of false-positive findings and we cross-validated the results between sets. Results Maternal folate intake was broadly associated with less child's DNA methylation: with a q-value Conclusions This study was the first to investigate the association between maternal folate intake during the peri-conception period and DNA methylation at birth with a genome-wide approach and it found numerous associations throughout the genome. The relationships between folate-sensitive CpG sites and DNA methylation events critical to childhood leukemogenesis will be considered in our subsequent research. Citation Format: Semira Gonseth, Ritu Roy, E. Andres Houseman, Adam de Smith, Mi Zhou, Seung-Tae Lee, Sébastien Nusslé, Amanda W. Singer, Margaret R. Wrensch, Catherine Metayer, Joseph L. Wiemels. Maternal folate intake at periconception and genome-wide DNA methylation modifications at birth in children. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2763. doi:10.1158/1538-7445.AM2015-2763 |
| Databáze: | OpenAIRE |
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