title: Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients.
abstract: APC/β-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/β-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2 × 2 factorial chemoprevention clinical trial of supplemental calcium (1200 mg daily) and vitamin D (1000 IU daily), alone and in combination versus placebo, we assessed APC, β-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and 1-yr follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D versus no vitamin D, the ratio of APC expression to β-catenin expression in the upper 40% (differentiation zone) of crypts (APC/β-catenin score) increased by 28% (P = 0.02), for calcium versus no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium versus calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D versus no vitamin D, 8% (P = 0.31) for calcium versus no calcium, and 12% (P = 0.21) for vitamin D + calcium versus calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Siyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Barry
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.|Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.|University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Division of Digestive Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Robin E
authors.initials: RE
authors.lastname: Rutherford
authors.affiliation: Consultants in Gastroenterology, West Columbia, South Carolina.
authors.forename: March E
authors.initials: ME
authors.lastname: Seabrook
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.|Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
mesh_terms: D000236:Adenoma / Q000473:pathology / Q000517:prevention & control*; D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D002136:Calcium, Dietary / Q000627:therapeutic use*; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000473:pathology*; D015398:Signal Transduction; D014807:Vitamin D / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use; D051176:beta Catenin / Q000032:analysis*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D015820:Cadherins; D002136:Calcium, Dietary; D014815:Vitamins; D051176:beta Catenin; D014807:Vitamin D
keywords: biological markers; calcium; clinical trial; colorectal neoplasms; vitamin D