TY - JOUR
T1 - Inflammation modulation by Vitamin D and Calcium in the morphologically normal colorectal mucosa of patients with colorectal adenoma in a clinical trial
AU - Gibbs, David Corley
AU - Fedirko, Veronika
AU - Baron, John A.
AU - Barry, Elizabeth L.
AU - Flanders, W. Dana
AU - McCullough, Marjorie L.
AU - Yacoub, Rami
AU - Raavi, Tapasya
AU - Rutherford, Robin E.
AU - Seabrook, March E.
AU - Bostick, Roberd M.
N1 - Funding Information:
This research was supported by the NCI of the NIH under award numbers F30CA236231 (to D.C. Gibbs), R01 CA114456 (to R.M. Bostick), and R01 CA098286 (to J.A. Baron); a Georgia Cancer Coalition Distinguished Scholar award (to R.M. Bostick); and the Anne and Wilson P. Franklin Foundation (to R.M. Bostick). Pfizer Consumer Healthcare provided the study agents.
Funding Information:
J.A. Baron reports grants from NCI during the conduct of the study; in addition, J.A. Baron has a patent for Chemopreventive Use of calcium issued (not currently licensed). E.L. Barry reports grants from NIH/NCI during the conduct of the study. W.D. Flanders owns Epidemiologic Research & Methods, LLC which does consulting work for clients. He knows of no conflicts. R.M. Bostick reports grants from NCI, NIH, grants from The Anne and Wilson P. Franklin Foundation, and Georgia Cancer Coalition Distinguished Scholar Award during the conduct of the study. No disclosures were reported by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. Wetested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group (P=0.001), 46%in the calciumgroup (P=0.002), and 34%in the calcium + vitamin D group (P = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoformDBP2 (GC rs4588∗A), the COX-2/ 15-HPDG ratio decreased 70% (P = 0.0006), 75% (P = 0.0002), and 60% (P = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorablymodulate thebalanceof expression of COX-2 and15- HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform).
AB - Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. Wetested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group (P=0.001), 46%in the calciumgroup (P=0.002), and 34%in the calcium + vitamin D group (P = 0.03), relative to the placebo group. Among individuals with the functional vitamin D-binding protein isoformDBP2 (GC rs4588∗A), the COX-2/ 15-HPDG ratio decreased 70% (P = 0.0006), 75% (P = 0.0002), and 60% (P = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorablymodulate thebalanceof expression of COX-2 and15- HPGD-biomarkers of inflammation that are strongly linked to colorectal carcinogenesis-in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform).
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U2 - 10.1158/1940-6207.CAPR-20-0140
DO - 10.1158/1940-6207.CAPR-20-0140
M3 - Article
C2 - 32917645
AN - SCOPUS:85100530930
SN - 1940-6207
VL - 14
SP - 65
EP - 76
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 1
ER -