Study of Folic Acid, Calcium and Vitamin D in Preventing Colorectal Polyps and Colorectal Cancer
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ABSTRACT:
DISEASE(S): Colorectal Neoplasms
PROVIDER: 2161109 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism. 5 groups of NTD mutants were studied. From each mutant group Heterozygous (test) and wild-type (control) female pups were used for this study at 6-8 weeks of age. 4 biological replicates were used for each of the test and control groups of each mutant. All mice used for the experiments were fasted 4-5 hours before dissection. A total of 36 samples were analyzed.
2013-09-30 | E-GEOD-51285 | biostudies-arrayexpress
Project description:Neural tube defects (NTDs) are serious birth defects with an estimated worldwide incidence of 1 per 1,000 live births. The multifactorial nature of NTDs in humans has made it difficult to elucidate pathogenesis mechanisms. However, a strong relationship has been established between folate-homocysteine metabolism and NTD risk. Prevention of a substantial proportion of fetal NTDs can be achieved through maternal folic acid (FA) supplementation. However the mechanism by which FA exerts its beneficial effect remains unclear. METHODS: To improve our understanding of the underlying mechanisms of NTD pathogenesis and the ways in which folate exerts its beneficial effect, we analyzed mRNA profiles as well as folate and vitamin B12 levels in five NTD mouse mutants whose response to dietary FA was previously established. RESULTS: Differentially expressed genes representing the effect of each NTD-causing mutation were identified and associated with biologic pathways. Interestingly, the panel of NTD mutants collectively revealed pathways related to two nuclear receptors, retinoid X receptor (RXR) and pregnane X receptor (PXR), suggesting that these pathways may be related to a shared mechanism of NTD development. Moreover, the NTD-causing mutations that were associated with FA responsiveness had expression profiles that were related to folate-homocysteine metabolic pathways. These pathways were not strongly associated with mutants that do not respond to FA supplementation, implying that FA may be beneficial when the NTD mutation affects pathways related to folate-homocysteine metabolism.
2013-09-30 | GSE51285 | GEO
Project description:Recent concerns have been raised regarding high folate intake during pregnancy and lactation, particularly following food fortification and increased vitamin supplement use. Epidemiologic studies have shown that high folic acid (FA) intake can negatively impact motor and neurocognitive development in offspring. We used microarray to investigate the mechanisms by which a supplemented diet containing 5-fold higher FA than recommended (FASD) affects brain function in both male and female offspring.
2024-03-03 | GSE134588 | GEO
Project description:Folic acid is present in pre-natal vitamins, fortified cereal grains and multi-vitamin supplements. High intake of folic acid through these sources has resulted in populations with increased levels of serum folate and unmetabolized folic acid. Although the benefits of folic acid in the prevention of neural tube defects are undeniable, the impact of long-term consumption of folic acid on the prostate is not fully understood. In this study, we used a rodent model to test whether dietary folic acid (FA) supplementation changes prostate homeostasis and response to androgen deprivation. Although intact prostate weights do not differ between diet groups, we made the surprising observation that dietary folic acid supplementation confers partial resistance to castration-mediated prostate involution. More specifically, male mice that were fed a folic acid supplemented diet and then castrated had greater prostate wet weights, greater prostatic luminal epithelial cell heights, and more abundant RNAs encoding prostate secretory proteins compared to mice that were fed a control diet and castrated. We used RNA-seq to identify signaling pathways enriched in the castrated prostates from folic acid supplemented diet fed mice compared to control mice. We observed differential expression of genes involved in several metabolic pathways in the FA supplemented mice. Together, our results show that dietary FA supplementation can impact metabolism in the prostate and attenuate the prostate’s response to androgen deprivation. This has important implications for androgen deprivation therapies used in the treatment of prostate disease, as consumption of high levels of folic acid could reduce the efficacy of these treatments.
2018-08-22 | GSE116299 | GEO
Project description:Recent concerns have been raised regarding high folate intake during pregnancy and lactation, particularly following food fortification and increased vitamin supplement use. Epidemiologic studies have shown that high folic acid (FA) intake can negatively impact motor and neurocognitive development in offspring. We used microarray to investigate the impact of a supplemented diet containing 5-fold higher FA than recommended (5xFASD) on cerebral transcription profile in both male and female postnatal day (P) 30 pups. We also studied gene expression changes due to sex.
2022-03-15 | GSE193355 | GEO
Project description:Food fortification of folic acid (FA) and increased use of vitamin supplements have raised concerns over high folate intake periconceptionally. We reported that diet containing 5-fold higher FA than recommended for mice (5xFASD) during pregnancy, resulted in neurobehavioral abnormalities (hyperactivity and short-term memory impairment) in newborns. Our goal was to determine the origins of these changes and the underlying mechanisms by examing potential transcription changes in E17.5 embryonic cerebrum. We used microarrays to compare the E17.5 cerebral gene expression changes by 5xFASD and indentified different transcription profiles due to diet or sex.
2022-03-15 | GSE193352 | GEO
Project description:Background & Aims: Previous studies have suggested that dietary folic acid (FA) can protect against certain types of cancers. However, the findings have varied and the mechanisms by which this vitamin exerts chemopreventive effects remain to be clarified. We examined the effects of FA supplementation on DNA methylation, gene expression and gastric dysplasia in a transgenic mouse model that is etiologically and histologically well matched with human gastric cancers. Methods: Hypergastrinemic mice (INS-GAS) infected with Helicobacter felis were studied at multiple stages of gastric dysplasia and early cancer, with FA supplementation initiated both at weaning and later in life. Global DNA methylation was assessed by a methylation-sensitive cytosine incorporation assay, bisulfite pyrosequencing of B1 repetitive elements and immunohistochemistry (IHC) with anti-5-methylcytosine. We also profiled gene expression in the same tissues. Results: We found a decrease in global DNA methylation and tissue folate and an increase in serum homocysteine with progression of gastric dysplasia. FA supplementation prevented this loss of global DNA methylation and markedly reduced gastric dysplasia and mucosal inflammation. FA protected against the loss of global DNA methylation both in the dysplastic gastric epithelial cells and in gastric stromal myofibroblasts. In addition, FA supplementation had an anti-inflammatory effect, as indicated by expression profiling and IHC for lymphocyte markers. Conclusions: We conclude that FA supplementation is chemopreventive in this model of Helicobacter-associated gastric cancer. The beneficial effect of FA is likely due to its ability to reverse global loss of methylation and suppress inflammation. Study the difference in gene expression between transgenic hypergastrinemic (INS-GAS) mice fed a folate-supplemented diet and a diet with normal folate content. Because folate had a substantial protective effect, we matched the animals not only by folate status but also by dysplasia score (DYS). The degree of dysplasia was scored on a 1-4 scale. True replicates are not included. The first five samples are from folate supplemented animals, and the latter five are from controls on regular chow.
2011-07-20 | E-GEOD-30830 | biostudies-arrayexpress
Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.
2015-11-16 | GSE74548 | GEO
Project description:Interventions: secondary prevention-FS:folic acid 0.8mg/day,sodium butyrate 700mg tid;primary prevention-control group:routine treatment;Group I-CV:calcium 1200mg/d vitamin D3 250 IU/d;primary prevention:folic acid 0.8mg/day;Group II-S:sodium butyrate 700mg tid;Group II-RT:therapeutic endoscopy and routine treatment;Group I-RT:routine treatment;Group II-FSCV:folic acid 0.8mg/day, sodium butyrate 700mg tid, c;Group II-CV:folic acid 0.8mg/day, sodium butyrate 700mg tid, c
Primary outcome(s): incidence of polypi or carcinom;serum calcium
Study Design: Randomized parallel controlled trial
| 2671330 | ecrin-mdr-crc
Project description:Folic acid is a nutrient essential for embryonic development. Folate deficiency can cause embryolethality or neural tube defects and orofacial anomalies. Folate receptor 1 (Folr1), is a folate binding protein that facilitates the cellular uptake of dietary folate. Animal studies highlighted critical roles of folate in embryogenesis including orofacial development. Orofacial clefts were observed in the offspring of experimental animals on folic acid-deficient diets. Mice lacking Folr1 (the gene encoding folate receptor 1) also demonstrated a variety of orofacial defects. In order to investigate potential roles of Folr1 during embryogenesis and to identify various genes functionally associated with this receptor, total RNA preparations from gestation day (GD)-9.5, Folr1+/+ and Folr1-/- mouse embryos were used to hybridize messenger RNA arrays, to identify genes expressed in wild type (Folr1+/+) and knockout (Folr1-/-) embryos.
2021-02-10 | GSE155428 | GEO