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Effects of calcium and vitamin D 3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: A randomized controlled trial
Author(s) -
Tu Huakang,
Flanders W. Dana,
Ahearn Thomas U.,
Daniel Carrie R.,
GonzalezFeliciano Amparo G.,
Long Qi,
Rutherford Robin E.,
Bostick Roberd M.
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22096
Subject(s) - vitamin d and neurology , colorectal adenoma , medicine , placebo , biology , transforming growth factor , vitamin , colorectal cancer , endocrinology , calcium , autocrine signalling , intestinal mucosa , adenoma , immunohistochemistry , vitamin d deficiency , gastroenterology , pathology , cancer , receptor , alternative medicine
Transforming growth factor alpha (TGFα) and TGFβ 1 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 3 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 D 3 800 IU/d versus placebo over 6 mo. TGFα and TGFβ 1 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 3 , and calcium plus vitamin D 3 groups relative to the placebo group (1) the mean overall expression of TGFβ 1 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/TGFβ 1 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 D 3 may increase TGFβ 1 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.