Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: A randomized, double- blinded, placebo-controlled clinical trial

Roberd M. Bostick, Lisa Fosdick, Patricia Grambsch, Greg A. Grandits, Thomas A. Louis, John D. Potter, James R. Wood, Tamera J. Lillemoe

Research output: Contribution to journalArticle

Abstract

Background: The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings in preliminary clinicaltrials have suggested similar effects in humans. Purpose: A randomized, double-blind, placebo-controlled, clinical trial was designed to determine whether calcium supplementation will reduce the colorectal epithelial cell proliferation rate and normalize the distribution of proliferating cells within colorectal crypts (i.e., shift the zone of proliferation from the entire crypt to the lower 60% of the crypt, which is thought to be the normal proliferative zone of the crypt) in patients with sporadic adenomas. Methods: Sporadic adenoma patients (n = 193) were treated with placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily for 6 months. Rectal mucosa biopsy specimens were obtained at base line and at 1-, 2-, and 6-month follow-up. Cell proliferation was measured by detection of S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. The cell proliferation rate, called labeling index (LI), was calculated as the proportion of labeled cells in the crypts. The deviation of the proliferative zone from the normal location in the lower 60% of the crypt was calculated as the proportion of labeled cells in the upper 40% of the crypt, called distributional index (øh). The effects of calcium treatment on the LI and øh were expressed as relative effects-(calcium follow-up/calcium base line)/(placebo follow-up/placebo base.line). Calculations and inference testing of the relative effects were accomplished using a repeated-measures mixed model on log-transformed LI and 0h values. All statistical tests were two-sided. Results: Scorable biopsy specimens were obtained on 170 patients at base line, 164 at 1 month, 161 at 2 months, and 163 at 6 months. The difference in the change in the LI between the combined calcium groups and the placebo group was insignificant, with a relative effect of calcium versus placebo of 0.97 (P =.87). However, for the 0h, the relative effect of calcium versus placebo was 0.50 (P =.05) in the combined calcium groups, 0.56 (P =.16) in the 1.0-g calcium group, and 0.44 (P=.05) in the 2.0-g calcium group. Conclusions: Calcium supplementation normalizes the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. Implications: These results support further study of whether alterations in colon cell proliferative kinetics represent true intermediate steps in colon carcino-genesis that can be used to investigate the etiology and prevention of, and whether a higher calcium consumption can reduce the risk of, colon cancer. [J Natl Cancer Inst 1995; 87: 1307-15]

Original languageEnglish (US)
Pages (from-to)1307-1315
Number of pages9
JournalJournal of the National Cancer Institute
Volume87
Issue number17
DOIs
StatePublished - Sep 6 1995
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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