The influence of folate supplementation on global gene expression in normal colonic mucosa of subjects with colorectal adenoma

Pufulete, Maria; Abbadi, Reyad; Arno, Matthew; Ewins, Mark; Green, Caroline; Astarloa, Estibaliz Aldecoa-Otalora; Sanders, Tom; Emery, Peter W.

doi:10.1002/mnfr.201200617

Cited by 4 publications

(9 citation statements)

References 47 publications

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“…Folic acid supplementation decreased methylation in c-myc and c-jun , thereby promoting the malignant phenotype of placental trophoblasts. Folic acid was observed to induce gene-specific positive and negative changes in promoter methylation and mRNA expression in our study, this is consistent with the earlier studies showing the dual effect of folic acid supplementation on the global gene expression in certain cancers ( 11 , 12 , 14 ). Additionally, folic acid dysregulation may affect gene expression also by inducing base substitution, DNA breaks, gene deletions, and gene amplification ( 49 ).…”

Section: Discussionsupporting

confidence: 93%

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Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

et al. 2022

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BackgroundOne of the unique features of placentation is its similarity to tumorigenesis yet being very well regulated. It allows rapid proliferation, migration, and invasion of mononuclear trophoblast cells into the maternal uterus and remodeling the maternal vasculature. This pseudomalignant nature of trophoblastic cells is strictly regulated and its importance becomes evident in abnormal pregnancies that are characterized by aberrant trophoblast proliferation/invasion like preeclampsia. In addition to this, the importance of folic acid supplementation during pregnancy is well documented. We aimed to analyze the molecular and epigenetic regulation of the pseudomalignant nature of placentation via folic acid levels.MethodsPlacental tissue samples were collected from different pregnancies in three different gestational stages. We estimated the impact of folic acid levels on global methylation, LINE1 methylation, and expression of DNMTs in all three gestational stages in pregnant women and preeclampsia pregnancies. We also analyzed the effect of folic acid supplementation on trophoblastic invasion using placental derived cells viz, JEG-3 and HTR-8/SVneo cell line and verified the molecular and epigenetic mechanisms involved in this regulation.ResultsDevelopment of preeclampsia was observed to be associated with lower folate levels in placental tissue, higher global methylation level, and higher expression of DNMT1and DNMT3A. Folic acid supplementation was found to increase the invasive potential of placental trophoblasts by almost two folds which were associated with the decreased expression of tumor suppressor genes and tissue inhibitors of matrix metalloproteinases; and increased expression of oncogenes, telomerase gene, and matrix metalloproteinases. These folic acid-mediated changes were observed to be regulated by CpG methylation in the case of many genes. Folic acid supplementation was also observed to significantly decrease global methylation in placental trophoblasts related to decreasing expression of DNMT1 and DNMT3A.ConclusionLower folic acid levels are associated with preeclampsia development and folic acid supplementation regulates the invasive potential of placental trophoblasts as mediated by various epigenetic changes in the placenta suggesting the protective effect of folic acid against preeclampsia.

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Section: Discussionsupporting

confidence: 93%

“…Further, folic acid supplementation is known to affect the transcription of various genes, with both enhancing and down regulating gene expression ( 11 , 12 ). is an association with its promoting or repressing effects on DNA and histone methylation ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

et al. 2022

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“…16 The epigenetic effects of folate supplementation in the presence of colorectal adenomas have been hypothesized. [17][18][19] In individuals with colorectal adenomas and normal folate levels at baseline, changes in tissue biomarkers associated with colon cancer in patients supplemented with folate have been assessed. P53 and DNA strand breaks in exons 5-8 demonstrated accelerated improvement over the first 6 months when compared with placebo, but this difference was not sustained on assessment at 1 year.…”

Section: B Vitaminsmentioning

confidence: 99%

“…Notably, there was no increase in adverse events in the supplemented group. 17 After considering the role of B vitamin supplementation in these scenarios, the route of administration may also be important. Specific to vitamin B 12 supplementation, there has been study of the efficacy of enteral vs intramuscular supplementation in patients following gastrectomy for gastric cancer.…”

Section: B Vitaminsmentioning

confidence: 99%

Micronutrient deficiencies in patients with gastrointestinal cancer: To treat or not to treat

Turkiewicz

García²,

Li³

et al. 2023

Nut in Clin Prac

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Nutrition supplements are widely used among patients with cancer. The general public perceives supplements as more natural anticancer and antitoxicity agents, and often supplements are used without the knowledge of the treating physician. In the clinical setting, there are concerns that supplements may decrease effectiveness of chemotherapy and/or radiotherapy and, as a result, supplementation is avoided. There is a body of literature evaluating micronutrient deficiencies, supplementation, and cancer risk; however, little is known about the risks of treatment of micronutrient deficiencies in specific cancers. Of the types of cancers, patients with gastrointestinal cancers are at high risk of developing malnutrition and, subsequently, possible micronutrient deficiencies. This review aims to evaluate the effects of supplementation of specific micronutrients in patients with cancer of the digestive tract.

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“…In fact, the altered DNA and RNA methylation, and the disruption of DNA integrity and repair, lead to DNA aberrations with a higher risk of developing cancers and in particularly the colorectal one [93]. Furthermore, the results of a randomized trial conducted on fourteen subjects with adenoma receiving 400 mcg/day or placebo for 10 weeks, indicated that folic acid can modify gene expression [94]. …”

Section: Folic Acidmentioning

confidence: 99%

Pharmacological and dietary prevention for colorectal cancer

et al. 2013

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BackgroundColorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics.DiscussionThe studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results.ConclusionThe results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be suggested to potentiate such effects by adding them together.

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The influence of folate supplementation on global gene expression in normal colonic mucosa of subjects with colorectal adenoma

Abstract: These results indicate that while folic acid can modify gene expression, it is difficult to separate its effects from the natural variability in gene expression in the colon.

Cited by 4 publications

References 47 publications

Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia

Micronutrient deficiencies in patients with gastrointestinal cancer: To treat or not to treat

Pharmacological and dietary prevention for colorectal cancer

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