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publicado em 02/01/2011 às 02h00:00
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High levels of folate in the blood increases suppression of genes that are silenced tumor

Study evaluated the association between folic acid and hypermethylation of DNA found in cancer and diseases of aging

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Researchers at the University of Texas MD Anderson Cancer Center, USA, found that people with high levels of folate in their red blood cells are more likely to have two suppressor genes turned off by methylation.

Hypermethylation of DNA is found in a variety of cancers and diseases of aging such as heart disease. Methyl groups attach to genes in locations called CpG islands and stand as markers or labels of the promoter region, preventing gene expression.

"Our new discovery is that having high levels of folate in the blood is related to greater levels of DNA methylation," said co-author, Jean-Pierre Issa.

Folate is a naturally occurring B vitamin that plays a role in the creation, repair and function of DNA, as well as the production of red blood cells.

Folate is found in leafy vegetables, fruits, beans and peas, and since 1998 its synthetic version, folic acid, was added to the manufacture of bread, cereals, flours, pasta, rice and other grains.

The effect of folate on cancer, thought to be primarily preventive, it became less clear in recent years, as scientists have found that promotional aspects of the disease with the intake of folate in colorectal cancer, prostate and other cancers .

The research team analyzed the association between blood levels of folate, dietary factors and lifestyle on DNA methylation in normal colorectal tissue. They followed 781 patients in a clinical trial comparing folate to aspirin in preventing pre-cancerous polyps.

They gathered demographic and lifestyle diet and compared the methylation of two suppressor genes between the first and performed a colonoscopy three years later.

Genes, it was and SFRP1 are expressed in normal colorectal tissue, but silenced by methylation in colon cancer. The two genes were also found to be methylated in prostate tumors, breast and lung.

Age was strongly associated with increased methylation - a finding that confirms the long-term research.

Neither treatment with folic acid nor aspirin were significantly associated with levels of methylation. However, RBC folate was associated with methylation of two genes with differences arising from other genes.

"These differences were not trivial, they showed the equivalent of 10 extra years of aging for those with high folate RBC count," said Issa. "Today, it is worrying that taking extra folic acid long term can lead to more DNA methylation, which then can lead to diseases potentially extras, including a greater likelihood of developing cancer and other diseases of aging."

Based on the results of the study, the researchers say the data for folate supplementation is now very ambiguous, and that people who take folic acid should think twice about it.

Moreover, they said, the findings, together with other data, should trigger a reassessment of the U.S. position that all people should take extra folic acid.


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methylation    folate    folic acid    gene deletion    Jean-Pierre Issa    University of Texas MD Anderson Cancer Center       
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