title: Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: a randomized controlled trial.
abstract: Transforming growth factor alpha (TGFα) and TGFβ1 are growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively, that may (1) affect risk for colorectal cancer and (2) be modifiable by anti-proliferative exposures. The effects of supplemental calcium and vitamin D3 on these two markers in the normal-appearing colorectal mucosa in humans are unknown. We conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92; 23/treatment group) of calcium 2 g and/or vitamin D3 800 IU/d versus placebo over 6 mo. TGFα and TGFβ1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-mo follow-up. In the calcium, vitamin D3 , and calcium plus vitamin D3 groups relative to the placebo group (1) the mean overall expression of TGFβ1 increased by 14% (P= 0.25), 19% (P = 0.17), and 22% (P = 0.09); (2) the ratio of TGFα expression in the upper 40% (differentiation zone) to that in the lower 60 (proliferation zone) of the crypts decreased by 34% (P = 0.11), 31% (P = 0.22), and 26% (P = 0.33); and (3) the TGFα/TGFβ1 ratio in the upper 40% of the crypts decreased by 28% (P = 0.09), 14% (P = 0.41), and 22% (P = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and vitamin D3 may increase TGFβ1 expression and shift TGFα expression downward from the differentiation to the proliferation zone in the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation in a larger clinical trial.
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; Molecules to Mankind Program, Laney Graduate School, Emory University, Atlanta, Georgia.
authors.forename: Huakang
authors.initials: H
authors.lastname: Tu
authors.forename: W Dana
authors.initials: WD
authors.lastname: Flanders
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Ahearn
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Daniel
authors.forename: Amparo G
authors.initials: AG
authors.lastname: Gonzalez-Feliciano
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: Robin E
authors.initials: RE
authors.lastname: Rutherford
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
mesh_terms: D000236:Adenoma / Q000473:pathology* / Q000517:prevention & control; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000517:prevention & control; D019587:Dietary Supplements / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D015291:Transforming Growth Factors / Q000032:analysis*
chemical_list: D016588:Anticarcinogenic Agents; D002136:Calcium, Dietary; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; D002762:Cholecalciferol; D015291:Transforming Growth Factors
keywords: calcium; colorectal neoplasms; transforming growth factor alpha (TGFα); transforming growth factor beta 1 (TGFβ1); vitamin D3