Abstract
Decreased apoptosis in the colon is potentially an early indicator of colon cancer risk and may be influenced by calcium and vitamin D. This report describes the associations of calcium intake and 25-hydroxyvitamin D levels with apoptosis in colorectal epithelium. Consecutive patients undergoing colonoscopies were recruited for a study designed to examine risk and etiologic factors for colorectal adenomas. Diet was assessed by food frequency questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were measured using an enzyme immunoassay. Apoptosis was scored from normal rectal mucosal pinch biopsies. Linear and logistic regression analyses were used to examine associations between calcium, serum vitamin D, and apoptotic scores. Data were available for 498 and 280 patients for the calcium and vitamin D analyses, respectively. Associations of calcium intake and vitamin D with apoptosis were modified by adenoma case-status. In an adjusted logistic regression model, patients with adenomas in the highest versus lowest tertile of dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI), 0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the highest level of 25-hydroxyvitamin D was associated with higher apoptosis in adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2). These results are consistent with a calcium and vitamin D-mediated apoptotic mechanism in colon carcinogenesis.
Highlights
Apoptosis is essential to maintaining the structure of the colorectal epithelial crypts by counterbalancing cellular proliferation
In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% confidence interval (CI), 0.6-2.7)
There is increasing evidence suggesting that calcium and vitamin D play important roles in reducing the risk of colorectal cancer
Summary
Apoptosis is essential to maintaining the structure of the colorectal epithelial crypts by counterbalancing cellular proliferation. There is evidence that a decreased level of apoptosis in the colorectal epithelium may be an early indicator of increased risk of adenoma development or colorectal cancer [1,2,3]. Calcium and vitamin D are biologically linked and both have shown promise as preventive agents of colorectal cancer [7,8,9,10,11]. Compared with mice on a standard diet of 0.5% calcium, increasing the concentration to 1.0% resulted in higher levels of apoptosis in the distal colorectal epithelium [12]. In human colorectal adenoma and cancer cell lines, the active metabolite of vitamin D [1,25 (OH)2D3] was found to induce apoptosis in a dose-dependent manner [13]
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