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High red blood cell folate levels linked to silenced tumor-suppressors
Date:12/22/2010

esearch team analyzed the association between folate blood levels and dietary and lifestyle factors on DNA methylation in normal colorectal tissue. They enrolled 781 patients from a parent clinical trial that compared folate to aspirin in the prevention of precancerous colorectal polyps.

They gathered demographic, lifestyle and dietary information and compared methylation of two tumor-suppressing genes between the first colonoscopy and one three years later.

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

Age was strongly associated with increased methylation a finding that confirmed longstanding research. Methylation levels also varied between the rectum and right colon and among different ethnic groups for each gene.

Neither folate nor aspirin treatment were significantly associated with methylation levels. However, RBC folate was associated with methylation of both genes with significant differences emerging between the top quarter of patients with the highest RBC folate count and the bottom quarter with the lowest. RBC folate levels closely reflect long-term folate intake.

"These differences were not trivial, they were the equivalent of 10 years of extra aging for those with high RBC folate counts," Issa said.

"Today it's worrisome that taking extra folate over the long term might lead to more DNA methylation, which then might lead to extra diseases including potentially an increased chance of developing cancer and other diseases of aging," Issa said.

"The data for folate supplementation right now are very ambiguous and I personally think people taking folate should think twice about it," Issa said. "Also, these findings, added to other data, should trigger a rethinking of the U.S. position that everyone should be taking extra folate."


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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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