New paper [1] that discusses PCa hypermethylation & (reversible) epigenetic changes. I have been interested for a dozen years, after vitamin B12 injections caused PSA to rise. But researchers seem slow to pursue this.
Most will want to skip the full text. But here is a snippet that touches on diet:
"DNA methyltransferase co-factor S-adenosyl methionine (SAM) is the source of methyl groups for DNA methylation. Following removal of the methyl group, SAM is converted to S- adenosyl homocysteine (SAH) and homocyste- ine. Homocysteine re-methylation to replenish pools of SAM requires several methyl group donors like methyl-folate, methionine and betaine. Availability of methyl donors in the diet can in uence DNA methylation. ...
"Dietary folate is a well-studied methyl donor. Folates are water soluble vitamins that partici- pate in one-carbon transfer, DNA synthesis, cell growth, hematopoiesis and metabolism. While folates occur naturally in the diet, folic acid is the synthetic form that is supplemented in forti- ed food stuffs or consumed as dietary supple- ments. Folates and folic acid are converted to 5-methyl tetrahydrofolate which provides meth- yl groups for the conversion of homocysteine to methionine. Methionine is converted to SAM, the methyl donor for DNA methylation reactions. Adequate consumption of folates is required to maintain SAM pools.
"In 1998, the United States mandated folic acid forti cation in cereal grains. Folic acid forti ca- tion has raised serum folate levels in popula- tions of several age groups, most signi cantly in children and older populations [166, 167]. In addition to participating in methylation, folates are important players in nucleotide biosynthe- sis and polyamine synthesis. The complex role of folates in the body could yield protective or deleterious effects depending on the context. High gestational folic acid has been shown to have adverse effects on offspring in rodent studies [168, 169]. Multiple clinical trials have associated folic acid supplement consumption with increased risk of prostate cancer [170- 172]. Moreover, studies in the TRAMP prostate cancer mouse model have shown that dietary folic acid deficiency can suppress tumor growth [173]. However, a few meta-analysis studies using combined data across multiple randomized trials have failed to identify an association between folic acid supplementation and prostate cancer risk [174, 175]."
"Despite contradictory data, the prevalence of folic acid supplement consumption warrants further research into the interaction between folic acid supplementation and prostate disease. Maternal supplementation, food grain forti cation and consumption of multi-vitamin supplements have resulted in populations that have been exposed to high levels of folic acid throughout their lifetime."
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"DNA methylation is at the con uence of the genome and environment."
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"We hope that this review can be used as an introduction to the eld by prostate researchers interested in studying DNA methylation."
-Patrick
[1] ajceu.us/files/ajceu0087776...
Abstract: Epigenetic mechanisms including DNA methylation are critical regulators of organismal development and tissue homeostasis. DNA methylation is the transfer of methyl groups to cytosines, which adds an additional layer of complexity to the genome. DNA methylation marks are recognized by the cellular machinery to regulate tran- scription. Disruption of DNA methylation with aging or exposure to environmental toxins can change susceptibility to disease or trigger processes that lead to disease. In this review, we provide an overview of the DNA methylation machinery. More speci cally, we describe DNA methylation in the context of prostate development, prostate cancer, and benign prostatic hyperplasia (BPH) as well as the impact of dietary and environmental factors on DNA methylation in the prostate.
... click on link for full text ...
Homocysteine, hypermethylation/PCa aggressiveness and MTFHR mutation
