Page 318 - Vitamin D and Cancer

13 Vitamin D and Colorectal Cancer 305

13.2 Colorectal Cancer Prevention with Vitamin D
Supplementation

13.2.1 Pathological Basis for Vitamin D Supplementation

Colonic normal, pre-cancerous, and cancerous epithelium may be targets to vitamin
D through a direct effect on vitamin D receptors (VDR) [69–73]. VDR expression
increases in the progression from normal mucosa to pre-malignant or malignant tis-
sue (aberrant crypt foci [ACF], polyps, and differentiated adenocarcinoma) [71, 73,
74]. Vitamin D 1a-hydroxylase, the enzyme responsible for the transformation of
25-D to the active form 1, 25-D , is expressed in colon tissue. The expression appears
3
3
equally prominent in normal, ACF, polyps, and differentiated colonic adenocarcino-
mas [73]. Recent reports, however, suggest that high grade tumors lose VDR and
vitamin D 1a-hydroxylase suggesting the importance of VDR and its activation in
maintaining normal tissue differentiation [75, 76]. While this may lessen the enthusi-
asm to investigate vitamin D compounds as antitumor agents in advanced colon
cancer, it suggests a window of potential opportunity for vitamin D compounds from
the early pre-ACF stage to the development of colon cancer (Fig. 13.4).

Fig. 13.4 Nuclear VDR staining for (a) Invasive cancer (b) Normal crypt (c) Tubular adenoma and
(d) Aberrant crypt foci