(1,25-D 3 ), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D 3 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D 3 , we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D 3 availability, decreasing its antiproliferative effect. (J Histochem Cytochem 58:277-285, 2010) COLORECTAL CANCER (CRC) is the second leading cause of malignant mortality in Western industrialized countries (Boyle and Ferlay 2005). Geographical distribution of cancer mortality in the US correlates with exposure to solar (ultraviolet B) radiation; the highest mortality rates for CRC were observed in regions with less solar radiation (Freedman et al. 2002). Furthermore, epidemiological data have shown an inverse association of serum 25-hydroxyvitamin D 3 (25-D 3 ) levels with risk for prostate, breast, and colorectal malignancies (Garland et al. 1989;Ahonen et al. 2000;Bertone-Johnson et al. 2005). Estimating premature cancer mortality in the US, Grant and Garland (2006) implied that actually 20-30% of CRC cases could be avoided by sufficient exposure to sunlight.A recent meta-analysis of 18 cohort and case-control studies showed that an elevation of serum 25-D 3 concentration to levels $33 ng/ml led to a 50% lower incidence of CRC (Gorham et al. 2005). Cumulative epidemiological evidence suggests that there is a direct correlation between reduced CRC incidence and sunlight exposure, nutritional vitamin D intake, and high serum levels of 25-D 3 (Giovannucci et al. 2006).Vitamin D metabolism is a strictly regulated, multistep process, beginning with the formation of previtamin D 3 in the skin, mediated by ultraviolet radiation, or with absorption of vitamin D from dietary sources (Henry 1997;Sawada et al. 2000;Cheng et al. 2003). Vitamin D is hydroxylated by CYP27A1 to 25-hydroxyvitamin D 3 in the liver. The last step of the activation is accomplished by the 25-hydroxyvitamin D 3 1a hydroxylase (CYP27B1) in the kidney. The most active metabolite of vitamin D 3, 1a,25-dyhydroxyvitamin D 3 (1,25-D 3 , also known as calcitriol), has a crucial Correspondence to: Enikö Kállay,

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Background: Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT) gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR) gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation.

Significant differences observed in gene expression profiles of osteoporotic and non-osteoporotic human bone tissues provide further insight into the pathogenesis of this disease. Characterization of the differences between osteoporotic and non-osteoporotic bones by expression profiling will contribute to the development of diagnostic tools in the future.

Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in the fibro-osseous lesions. The aim of our investigation was to identify genes that are differently expressed in fibrous versus non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from female patients with fibrous dysplastia (FD) and seven bone tissue samples from women without FD (non-FD) were examined. The expression differences of selected 118 genes were analyzed by the TaqMan probe-based quantitative real-time RT-PCR system. The Mann-Whitney U-test indicated marked differences in the expression of 22 genes between FD and non-FD individuals. Nine genes were upregulated in FD women compared to non-FD ones and 18 genes showed a downregulated pattern. These altered genes code for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines, and lipid metabolism-affected substrates. Canonical variates analysis demonstrated that FD and non-FD bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. The remarkable changed gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.