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- Title
Relative Expression of Vitamin D Hydroxylases, CYP27B1 and CYP24A1, and of Cyclooxygenase-2 and Heterogeneity of Human Colorectal Cancer in Relation to Age, Gender, Tumor Location, and Malignancy: Results from Factor and Cluster Analysis.
- Authors
Brozek, Wolfgang; Manhardt, Teresa; Kállay, Enikö; Peterlik, Meinrad; Cross, Heide S.
- Abstract
Previous studies on the significance of vitamin D insufficiency and chronic inflammation in colorectal cancer development clearly indicated that maintenance of cellular homeostasis in the large intestinal epithelium requires balanced interaction of 1,25-(OH)2D3 and prostaglandin cellular signaling networks. The present study addresses the question how colorectal cancer pathogenesis depends on alterations of activities of vitamin D hydroxylases, i.e., CYP27B1-encoded 25-hydroxyvitamin D-1α-hydroxylase and CYP24A1-encoded 25-hydroxyvitamin D-24-hydroxylase, and inflammation-induced cyclooxygenase-2 (COX-2). Data from 105 cancer patients on CYP27B1, VDR, CYP24A1, and COX-2 mRNA expression in relation to tumor grade, anatomical location, gender and age were fit into a multivariate model of exploratory factor analysis. Nearly identical results were obtained by the principal factor and the maximum likelihood method, and these were confirmed by hierarchical cluster analysis: Within the eight mutually dependent variables studied four independent constellations were found that identify different features of colorectal cancer pathogenesis: (i) Escape of COX-2 activity from restraints by the CYP27B1/VDR system can initiate cancer growth anywhere in the colorectum regardless of age and gender; (ii) variations in COX-2 expression are mainly responsible for differences in cancer incidence in relation to tumor location; (iii) advancing age has a strong gender-specific influence on cancer incidence; (iv) progression from well differentiated to undifferentiated cancer is solely associated with a rise in CYP24A1 expression.
- Subjects
AUSTRIA; VITAMIN D; INFLAMMATION; PATHOLOGY; CALCIUM regulating hormones; ANTI-inflammatory agents; CARCINOGENESIS; CARCINOGENICITY; ACADEMIC medical centers; AGE distribution; BIOPSY; CHI-squared test; COLON tumors; CONFIDENCE intervals; STATISTICAL correlation; MEDICAL records; MULTIVARIATE analysis; POLYMERASE chain reaction; RECTUM tumors; SEX distribution; STATISTICS; T-test (Statistics); TUMOR classification; VITAMIN D deficiency; DATA analysis; EQUIPMENT &; supplies; RETROSPECTIVE studies; REVERSE transcriptase polymerase chain reaction; DATA analysis software; DISEASE complications
- Publication
Cancers, 2012, Vol 4, Issue 3, p763
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers4030763