Article

Vitamin D and Prevention of Cancer - Ready for Prime Time?

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
New England Journal of Medicine (Impact Factor: 54.42). 03/2011; 364(15):1385-7. DOI: 10.1056/NEJMp1102022
Source: PubMed

ABSTRACT Given that the potential role of vitamin D in cancer prevention has been widely touted, many people were surprised that cancer-related considerations didn't figure prominently in the new Dietary Reference Intakes for vitamin D established by the Institute of Medicine (IOM).(1) An IOM committee on which we served, charged with determining the population needs for vitamin D in North America, reviewed the evidence linking vitamin D with both skeletal and nonskeletal health outcomes. The committee concluded that vitamin D plays an important role in bone health and that the evidence provides a sound basis for determining the population's needs. For . . .

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    • "However, most of the clinical data stem from observational studies. These studies consistently show a likely benefit for vitamin D supplementation in colon and breast cancer, but randomized clinical trial data of sufficient size and duration with sufficient doses of vitamin D to be definitive are lacking (Chung et al., 2011; Manson et al., 2011). Development of an analog with tissue specificity relative to effects on calcium absorption/bone resorption would enhance the chances of success in treating malignancies. "
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    ABSTRACT: Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.
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    • "The impact of calcium and vitamin D on breast and colorectal cancer is being intensively researched during the last ten years, but, up to this point, no definite answers can be given about these relations (Lin et al., 2007; Lappe et al., 2007; Manson et al., 2011). "
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    • "Previous data showed that a relatively noncalcemic analogue of vitamin D, 1-alpha-hydroxy-24-ethyl-cholecal- ciferol, is a promising chemopreventive agent in experimental mammary carcinogenesis models (Hussain et al. 2006). Until now, the research data have been inconsistent and do not help to establish a cause-effect relationship (Colston 2008; Chung et al. 2009; Manson et al. 2011). As shown in previous studies, we confirm that there is no correlation between the presence of VDR and ER/PR (Freake et al. 1984; Ulmann et al. 1984; Berger et al. 1987). "
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    ABSTRACT: In this study, we analyzed vitamin D receptor (VDR) expression and survival in a breast cancer patient cohort of 82 breast cancer patients. Immunohistochemical analysis was possible in 91.5% of the patients (75/82). Staining was evaluated using the semi-quantitative assay according to Remmele and Stegner (immunoreactivity score [IRS]). IRS 0-1 was negative/very low, IRS 2-4 was moderate to high, and IRS 6-12 was high. Statistical analysis was performed by Spearman's correlation test (p<0.05 significant). Overall survival was analyzed using Kaplan-Meier estimations. Only 6 patients had a negative IRS. Moderate IRS values were present in 20 patients. Most of the patients had a high IRS (49). For survival analysis, data were dichotomized (IRS 0-4: negative to moderate and IRS 6-12: high VDR expression). In univariate analysis, VDR expression showed significant differences in progression-free survival (PFS) and overall survival (OS). Patients with high IRS scores showed significantly better PFS and OS than patients with moderate/negative IRS scores for VDR expression. Tumor size was significantly correlated to PFS. When analyzed separately, the three different IRS groups showed significant differences in VDR expression. The present data suggest that VDR expression in breast cancer tissue may be of clinical significance, and the results provide evidence that VDR may be a factor with prognostic relevance.
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