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

S. L. OReilly, A. P. McGlynn, Helene McNulty, J. Reynolds, G. R. Wasson, A. M. Molloy, JJ Strain, D. G. Weir, M Ward, G. McKerr, J. M. Scott, Stephen Downes

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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/m2) 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/105 cells to 18.1 ± 2.12 pg/105 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.
Original languageEnglish
Pages (from-to)933-939
Number of pages7
JournalJournal of Nutrition
Volume146
Issue number5
DOIs
Publication statusPublished - 13 Apr 2016

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Polyps
Folic Acid
Randomized Controlled Trials
Biomarkers
DNA
Uracil
Adenomatous Polyps
Colonoscopy
Mucous Membrane
Placebos
Comet Assay
Tumor Biomarkers
Carcinogenesis
Body Mass Index

Keywords

  • colon cancer
  • colonocyte
  • folate
  • uracil misincorporation
  • DNA methylation
  • field cancerization

Cite this

OReilly, S. L. ; McGlynn, A. P. ; McNulty, Helene ; Reynolds, J. ; Wasson, G. R. ; Molloy, A. M. ; Strain, JJ ; Weir, D. G. ; Ward, M ; McKerr, G. ; Scott, J. M. ; Downes, Stephen. / 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. In: Journal of Nutrition. 2016 ; Vol. 146, No. 5. pp. 933-939.
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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",
abstract = "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/m2) 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/105 cells to 18.1 ± 2.12 pg/105 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.",
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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. / OReilly, S. L.; McGlynn, A. P.; McNulty, Helene; Reynolds, J.; Wasson, G. R.; Molloy, A. M.; Strain, JJ; Weir, D. G.; Ward, M; McKerr, G.; Scott, J. M.; Downes, Stephen.

In: Journal of Nutrition, Vol. 146, No. 5, 13.04.2016, p. 933-939.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - OReilly, S. L.

AU - McGlynn, A. P.

AU - McNulty, Helene

AU - Reynolds, J.

AU - Wasson, G. R.

AU - Molloy, A. M.

AU - Strain, JJ

AU - Weir, D. G.

AU - Ward, M

AU - McKerr, G.

AU - Scott, J. M.

AU - Downes, Stephen

PY - 2016/4/13

Y1 - 2016/4/13

N2 - 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/m2) 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/105 cells to 18.1 ± 2.12 pg/105 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.

AB - 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/m2) 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/105 cells to 18.1 ± 2.12 pg/105 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.

KW - colon cancer

KW - colonocyte

KW - folate

KW - uracil misincorporation

KW - DNA methylation

KW - field cancerization

UR - https://pure.ulster.ac.uk/en/publications/folic-acid-supplementation-in-postpolypectomy-patients-in-a-rando-3

U2 - 10.3945/jn.115.222547

DO - 10.3945/jn.115.222547

M3 - Article

VL - 146

SP - 933

EP - 939

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 5

ER -