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Folic acid supplementation in postpolypectomy patients in a randomized controlled trial increases tissue folate concentrations and reduces aberrant DNA biomarkers in colonic tissues adjacent to the former polyp site

O'Reilly, Sharleen L., McGlynn, Angela P., McNulty, Helene, Reynolds, John, Wasson, Gillian R., Molloy, Anne M., Strain, JJ, Weir, Donald G., Ward, Mary, McKerr, George, Scott, John M. and Downes, C. Stephen 2016, Folic acid supplementation in postpolypectomy patients in a randomized controlled trial increases tissue folate concentrations and reduces aberrant DNA biomarkers in colonic tissues adjacent to the former polyp site, Journal of nutrition, vol. 146, no. 5, pp. 933-939, doi: 10.3945/jn.115.222547.

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Title Folic acid supplementation in postpolypectomy patients in a randomized controlled trial increases tissue folate concentrations and reduces aberrant DNA biomarkers in colonic tissues adjacent to the former polyp site
Author(s) O'Reilly, Sharleen L.ORCID iD for O'Reilly, Sharleen L. orcid.org/0000-0003-3547-6634
McGlynn, Angela P.
McNulty, Helene
Reynolds, John
Wasson, Gillian R.
Molloy, Anne M.
Strain, JJ
Weir, Donald G.
Ward, Mary
McKerr, George
Scott, John M.
Downes, C. Stephen
Journal name Journal of nutrition
Volume number 146
Issue number 5
Start page 933
End page 939
Total pages 7
Publisher American Society for Nutrition
Place of publication Rockville, Md.
Publication date 2016-05
ISSN 0022-3166
1541-6100
Keyword(s) DNA methylation
colon cancer
colonocyte
field cancerization
folate
uracil misincorporation
Science & Technology
Life Sciences & Biomedicine
Nutrition & Dietetics
COLORECTAL-CANCER
METHYLENETETRAHYDROFOLATE REDUCTASE
EPITHELIAL-CELLS
CLINICAL-TRIAL
GLOBAL DNA
RISK
ADENOMAS
PLASMA
Summary BACKGROUND: Low folate status is associated with an increased risk of colorectal carcinogenesis. Optimal folate status may be genoprotective by preventing uracil misincorporation into DNA and DNA hypomethylation. Adenomatous polyps have low folate status compared with normal colonic mucosa, and they are surrounded by histologically normal mucosa that also is of low folate status. OBJECTIVE: In a randomized controlled trial conducted at a single Dublin hospital between April 2002 and March 2004, we assessed the effect of folic acid supplementation on tissue folate, uracil misincorporation into DNA, and global DNA hypomethylation in colonocytes isolated from sites of adenomatous polyps and from histologically normal tissue adjacent and 10-15 cm distal to them. METHODS: Twenty patients with adenomatous polyps on initial colonoscopy and polypectomy were randomly assigned to receive either 600 μg folic acid/d [n = 12, 38% men, mean age 64.3 y, and body mass index (BMI, in kg/m(2)) 26.6] or placebo (n = 8, 50% men, mean age 68.4 y, and BMI 27.2) for 6 mo, and then repeat the colonoscopy. Blood and colonocyte tissue folate concentrations were measured with the use of a microbiological assay. Uracil misincorporation and global DNA hypomethylation were measured in colonocytes with the use of modified comet assays. RESULTS: Over time, folic acid supplementation, compared with placebo, increased tissue folate (mean ± SEM) from 15.6 ± 2.62 pg/10(5) cells to 18.1 ± 2.12 pg/10(5) cells (P < 0.001) and decreased the global DNA hypomethylation ratio from 1.7 ± 0.1 to 1.0 ± 0.1 (P < 0.001). The uracil misincorporation ratio decreased by 0.5 ± 0.1 for the site adjacent to the polyp over time (P = 0.05). CONCLUSION: A response to folic acid supplementation, which increased colonocyte folate and improved folate-related DNA biomarkers of cancer risk, was seen in the participants studied. Exploratory analysis points toward the area formerly adjacent to polyps as possibly driving the response. That these areas persist after polypectomy in the absence of folate supplementation is consistent with a potentially carcinogenic field's causing the appearance of the polyp.
Language eng
DOI 10.3945/jn.115.222547
Field of Research 090899 Food Sciences not elsewhere classified
1111 Nutrition And Dietetics
0702 Animal Production
0908 Food Sciences
Socio Economic Objective 920411 Nutrition
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, American Society for Nutrition
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30084693

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.