Endocrine Abstracts

Background: Vitamin D prevents proliferation, promotes differentiation and induces apoptosis of colonic cells. A reduced dietary intake is associated with an increased risk of colorectal cancer (CRC). Recently, we have shown that 25-hydroxyvitamin D-1-alpha hydroxylase (1aOHase) mRNA, which converts vitamin D to its active metabolite, is upregulated in CRC. However, this was based on small number of samples and data on vitamin D receptor (VDR) expression in CRC are inconsistent.
Methods: Ethics approval and informed consent were gained. Real time RT-PCR assays were used to quantify absolute VDR mRNA and 1aOHase mRNA levels in the colonic mucosa from normal patients without malignancy (n=50) and from 49 paired normal colon and cancer samples.
Result: Median 1aOHase mRNA levels were higher in the tumours than in the paired normal samples (4.0x10⁶ vs. 1.1x10⁶ copies/micrograms total RNA respectively, P<0.0001). There was no significant difference between the tumour samples and normal mucosa from patients without cancer (4.0x10⁶ vs. 5.87x10⁶ copies/micrograms total RNA respectively). Amongst all samples, 1aOHase levels were higher (>3 fold) in 70% of tumours compared to paired normal samples.
In contrast, median VDR mRNA levels were reduced in tumours compared either to paired normal colon (6.8x10⁴ vs. 9.82x10⁴ copies/micrograms total RNA respectively, P<0.0001) or to samples from patients without cancer (6.8x10⁴ vs. 1.5x10⁵ copies/micrograms total RNA respectively, P<0.0001). There was no significant difference between VDR levels in normal samples adjacent to tumour and samples from patients without cancer.
Conclusions: The demonstration of local expression of both 1aOHase and VDR in the colon suggests that the colon is not only a target site for endocrine effects but also for production of active vitamin D. The reduced 1aOHase mRNA levels coupled with increased VDR expression in adjacent normal mucosa would suggest a dysregulation of the vitamin D endocrine axis in colorectal cancer patients.