Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort

Bae, Sajin; Ulrich, Cornelia M.; Bailey, Lynn B.; Malysheva, Olga; Brown, Elissa C.; Maneval, David R.; Neuhouser, Marian L.; Cheng, Ting‐Yuan David; Miller, Joshua W.; Zheng, Yingye; Xiao, Liren; Hou, Lifang; Song, Xiaoling; Buck, Katharina; Beresford, Shirley A.A.; Caudill, Marie A.

doi:10.4161/epi.27323

Cited by 38 publications

(30 citation statements)

References 40 publications

(56 reference statements)

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“…First, the recruitment for the Women's Health Initiative Observational Study spanned periods before (1994‐1995), during (1996‐1997), and after (1998) nationally mandatory folic acid fortification, which led to an upshift in folate status . Thus, the expression of FOCM genes and their influences on CRC risks might have been modified in the era of folic acid fortification . Second, a certain number of false‐positive results might have occurred when we investigated the gene‐nutrient interactions even though we implemented several measures to minimize this possibility.…”

Section: Discussionmentioning

confidence: 99%

Folate‐mediated one‐carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women's Health Initiative Observational Study

Cheng

Makar

Neuhouser

et al. 2015

Cancer

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Background Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions in relation to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. We comprehensively investigated associations between genetic variants in FOCM and CRC risk, and whether FOCM nutrient status modified these associations. Methods We genotyped 288 candidate and tagging single nucleotide polymorphisms (SNPs) in 30 FOCM genes among 821 incident CRC case-control matched pairs in the Women’s Health Initiative Observational Study cohort. FOCM biomarkers (red blood cell [RBC] folate, plasma folate, pyridoxal-5’-phosphate [PLP], vitamin B12, and homocysteine) and self-reported alcohol consumption were measured at baseline. Conditional logistic regression was implemented; effect modification was examined based on known enzyme-nutrient relationships. Results We observed statistically significant associations between CRC risk and functionally defined candidate SNPs of MTHFD1 (K134R), MTRR (P450R), and PRDM2 (S450N), and a literature candidate SNP of TYMS (g.676789A>T) (nominal P<0.05). In addition we noted suggestive associations for tagSNPs in CBS, DHFR, DNMT3B, MAT1A, MTHFD1, and MTRR (nominal P<0.05; non-significant adjusted P). Significant interactions between nutrient biomarkers and candidate polymorphisms were observed for (i) plasma/RBC folate and FOLH1, PON1, TCN2, DNMT1, and DNMT3B; (ii) plasma PLP and TYMS TS3; (iii) plasma B12 and BHMT2; (iv) homocysteine and MTHFR and AARS. Conclusions Genetic variants in FOCM genes are associated with CRC risk among postmenopausal women. FOCM nutrients continue to emerge as effect modifiers of genetic influences on CRC risk.

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Section: Discussionmentioning

confidence: 99%

Folate‐mediated one‐carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women's Health Initiative Observational Study

Cheng

Makar

Neuhouser

et al. 2015

Cancer

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“…Age and sex were included since they are commonly known to influence gene methylation. Folate level was included as different levels of folate status could confound the ability to produce methyl donors [33] and WHR was included as this has been identified as a strong factor that influences insulin resistance in SGA users [17] . A statistically significant result was set at p < 0.05 and analyses were ran using R version 3.1.0.…”

Section: Methodsmentioning

confidence: 99%

DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder

et al. 2015

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Aims This study aimed to assess the effect of second-generation antipsychotic (SGA) use and insulin resistance on a global measure of DNA methylation in patients diagnosed with bipolar disorder. Materials & Methods Subjects stable on medication (either mood stabilizer monotherapy or adjuvant SGAs) were assessed for insulin resistance. Global methylation levels were assessed in leukocyte DNA from whole blood using the Luminometric Methylation Assay. Multivariable linear regression was used to investigate the effect of insulin resistance and SGA use on DNA methylation. Results A total of 115 bipolar I subjects were included in this study. The average age was 43.1 ±12.2 years and 73% were on SGAs. Average% global methylation was 77.0 ± 3.26 and was significantly influenced by insulin resistance, SGA use and smoking. Conclusion This is the first study to show a relationship between SGA use, insulin resistance and global DNA methylation. Further work will be needed to identify tissue- and gene-specific methylation changes.

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“…Two studies reported a statistically significant positive correlation between higher blood folate levels and higher LINE-1 levels [37, 52]. However, in one of the same studies, folate intake from natural foods and total dietary folate equivalents were not found to be associated with higher LINE-1 levels [37].…”

Section: Resultsmentioning

confidence: 99%

Relationships between Global DNA Methylation in Circulating White Blood Cells and Breast Cancer Risk Factors

Chopra-Tandon

Arcaro

et al. 2017

Journal of Cancer Epidemiology

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It is not yet clear whether white blood cell DNA global methylation is associated with breast cancer risk. In this review we examine the relationships between multiple breast cancer risk factors and three markers of global DNA methylation: LINE-1, 5-mdC, and Alu. A literature search was conducted using Pubmed up to April 1, 2016, using combinations of relevant outcomes such as “WBC methylation,” “blood methylation,” “blood LINE-1 methylation,” and a comprehensive list of known and suspected breast cancer risk factors. Overall, the vast majority of reports in the literature have focused on LINE-1. There was reasonably consistent evidence across the studies examined that males have higher levels of LINE-1 methylation in WBC DNA than females. None of the other demographic, lifestyle, dietary, or health condition risk factors were consistently associated with LINE-1 DNA methylation across studies. With the possible exception of sex, there was also little evidence that the wide range of breast cancer risk factors we examined were associated with either of the other two global DNA methylation markers: 5-mdC and Alu. One possible implication of the observed lack of association between global WBC DNA methylation and known breast cancer risk factors is that the association between global WBC DNA methylation and breast cancer, if it exists, is due to a disease effect.

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Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort

Cited by 38 publications

References 40 publications

Folate‐mediated one‐carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women's Health Initiative Observational Study

Folate‐mediated one‐carbon metabolism genes and interactions with nutritional factors on colorectal cancer risk: Women's Health Initiative Observational Study

DNA methylation, insulin resistance and second-generation antipsychotics in bipolar disorder

Relationships between Global DNA Methylation in Circulating White Blood Cells and Breast Cancer Risk Factors

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