Calcium, Vitamin D, and Apoptosis in the Rectal Epithelium

Abstract

Objective: 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. Methods: 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.Results: 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).

Meta-Analyses of Vitamin D Intake, 25-Hydroxyvitamin D Status, Vitamin D Receptor Polymorphisms, and Colorectal Cancer Risk

“…Vitamin D status modulates various genes in the colorectal mucosa that may influence the cancer risk (71,80). In humans, vitamin D may induce the differentiation and apoptosis (81,82), both in colorectal adenoma or cancer cells (83) and in the normal colorectal epithelium (84)(85)(86).…”

Colorectal Mucosal Expression of MSH2 as a Potential Biomarker of Risk for Colorectal Neoplasms

“…It is a multifactorial disease that appears to be the result of interacting lifestyle and genetic factors (2)(3)(4)(5)(6)(7)(8)(9). The adenomatous polyp, the precursor to the vast majority of socalled "sporadic" colorectal cancer, currently is the only accepted reliable biomarker of risk for colorectal cancer (8,9), and its removal markedly reduces risk of cancer development.…”

One Disease, Two Lives

“…The lower the level, the higher the risk. The levels of 25-OH-D in Grau et al (2003), Jacobs et al (2006), Miller et al (2005, and Peters et al (2004) demonstrated a significant colorectal cancer or adenoma risk reduction in the range of 27-39.4 ng/ml, with a median of 33 ng/ml. Such a level is well within the normal range of 32-100 ng/ml for 25-OH-D levels.…”

“…Jacobs et al (2006) examined the sample cohort originating from the Ursodeoxycholicacid Trial for adenoma prevention and found a moderate, non-significant inverse association between 25-OH-D levels and adenoma recurrence. Interestingly, Miller et al (2005) revealed that higher 25-OH-D levels were associated with higher rectal epithelium apoptosis for patients with or without adenomas. Peters et al (2004) conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial.…”

“…colorectal epithelium apoptosis (Diaz, Paraskeva, Thomas, Binderup, & Hague, 2000;Miller et al, 2005). An effective dosage of vitamin D to raise 25-OH-D levels above 80 nmol/L (32 ng/ml) is critical in achieving cancer risk reduction.…”