Dataset Information

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

ABSTRACT: BACKGROUND:There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS:After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS:Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.

SUBMITTER: Perrier F

PROVIDER: S-EPMC6444439 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

Perrier F F Viallon V V Ambatipudi S S Ghantous A A Cuenin C C Hernandez-Vargas H H Chajès V V Baglietto L L Matejcic M M Moreno-Macias H H Kühn T T Boeing H H Karakatsani A A Kotanidou A A Trichopoulou A A Sieri S S Panico S S Fasanelli F F Dolle M M Onland-Moret C C Sluijs I I Weiderpass E E Quirós J R JR Agudo A A Huerta J M JM Ardanaz E E Dorronsoro M M Tong T Y N TYN Tsilidis K K Riboli E E Gunter M J MJ Herceg Z Z Ferrari P P Romieu I I

Clinical epigenetics 20190402 1

<h4>Background</h4>There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquir ...[more]

PMID: 30940212

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Project description:BackgroundPericonceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relation by food sources compared with folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known.ObjectivesWe evaluated the relation between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study.MethodsGenome-wide DNA methylation status obtained from archived neonatal blood spots from pediatric ALL cases (n = 189) and controls (n = 205) in the California Childhood Leukemia Study (CCLS) from 1995-2008 was compared with periconceptional folate from total, food, and supplemental sources using multivariable linear regression. Further stratification was performed by income, education, ethnicity, and total folate intake. We evaluated variable DNA methylation response to periconceptional folate by ALL case status through an interaction term.ResultsTwo significant differentially methylated probes (DMPs) were associated with food and supplemental periconceptional folate intake in all subjects (n = 394). The top differentially methylated region at the promoter region of DUSP22(dual specificity phosphatase 22) demonstrated DNA hypermethylation in ALL cases but not in controls in response to total and food folate intake. We further identified 8 interaction term DMPs with variable DNA methylation response to folate intake by ALL case status. Further stratification of the cohort by education and ethnicity revealed a substantially higher number of DMPs associated with supplemental folic acid intake in Hispanic subjects with lower income and educational level.ConclusionsWe identified modest associations between periconceptional folate intake and DNA methylation differing by source, including variation by ALL case status. Hispanic subjects of lower income and education appear uniquely responsive to periconceptional folate supplementation.

Project description:Study questionTo what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception?Summary answerPreconception dietary folate intake was positively associated with fecundability in a monotonic pattern.What is known alreadySupplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability.Study design, size, durationA prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020.Participants/materials, setting, methodsWe used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders.Main results and the role of chanceCompared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16).Limitations, reasons for cautionIt is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet.Wider implications of the findingsRecommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability.Study funding/competing interest(s)The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests.Trial registration numberN/A.

Dataset Information

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

Publications

Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.

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