title: Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial.
abstract: The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: W Dana
authors.initials: WD
authors.lastname: Flanders
authors.forename: Marjorie L
authors.initials: ML
authors.lastname: McCullough
authors.forename: Eduard
authors.initials: E
authors.lastname: Sidelnikov
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Daniel
authors.forename: Robin E
authors.initials: RE
authors.lastname: Rutherford
authors.forename: Aasma
authors.initials: A
authors.lastname: Shaukat
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000236:Adenoma / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002119:Calcium Carbonate / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000627:therapeutic use; D002762:Cholecalciferol / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects*; D007414:Intestinal Neoplasms / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002136:Calcium, Dietary; D002762:Cholecalciferol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D002119:Calcium Carbonate