Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: A randomized controlled trial. Issue 4 (26th October 2013)

• Record Type: Journal Article
• Authors: Tu, Huakang; Flanders, W. Dana; Ahearn, Thomas U.; Daniel, Carrie R.; Gonzalez‐Feliciano, Amparo G.; Long, Qi; Rutherford, Robin E.; Bostick, Roberd M.
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 4(2015:Apr.)
• Page Start: 270
• Page End: 280
• Publication Date: 2013-10-26
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22096
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mc22096-sec-0001" sec-type="section"> <p>Transforming growth factor alpha (TGFα) and TGFβ<sub>1</sub> 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 D<sub>3</sub> 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 (<italic>n</italic> = 92; 23/treatment group) of calcium 2 g and/or vitamin D<sub>3</sub> 800 IU/d versus placebo over 6 mo. TGFα and TGFβ<sub>1</sub> 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 D<sub>3</sub>, and calcium plus vitamin D<sub>3</sub> groups relative to the placebo group (1) the mean overall expression of TGFβ<sub>1</sub> increased by 14% (<italic>P</italic> = 0.25), 19% (<italic>P</italic> = 0.17), and 22% (<italic>P</italic> = 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% (<italic>P</italic> = 0.11), 31% (<italic>P</italic> = 0.22), and 26% (<italic>P</italic> = 0.33); and (3) the TGFα/TGFβ<sub>1</sub> ratio in the upper 40% of the crypts decreased by 28% (<italic>P</italic> = 0.09), 14% (<italic>P</italic> = 0.41), and 22% (<italic>P</italic> = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and vitamin D<sub>3</sub> may increase TGFβ<sub>1</sub> 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. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>