1Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla CA, U.S.A.
2Naval Health Research Center, San Diego, CA, U.S.A.
3Department of Epidemiology and Biostatistics, Graduate School of Public Health, San Diego State University, San Diego CA, U.S.A.
4Department of Surgery, School of Medicine, University of California San Diego, La Jolla CA, U.S.A.
Abstract Background: Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with a high risk of breast cancer. Since publication of the most current meta-analysis of 25(OH)D and breast cancer risk, two new nested case–control studies have emerged. Materials and Methods: A PubMed search for all case–control studies on risk of breast cancer by 25(OH)D concentration identified 11 eligible studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs. lowest quantile of 25(OH)D across all studies. Results: The overall Peto odds ratio summarizing the estimated risk in the highest compared to the lowest quantile across all 11 studies was 0.61 (95% confidence interval 0.47, 0.80). Conclusion: This study supports the hypothesis that higher serum 25(OH)D levels reduce the risk of breast cancer. According to the review of observational studies, a serum 25(OH)D level of 47 ng/ml was associated with a 50% lower risk of breast cancer.
Model Selection Approach Suggests Causal Association between 25-Hydroxyvitamin D and Colorectal Cancer
Lina Zgaga equal contributor mail, Felix Agakov equal contributor, Evropi Theodoratou, Susan M. Farrington, Albert Tenesa, Malcolm G. Dunlop,Paul McKeigue,Harry Campbell
Introduction Vitamin D deficiency has been associated with increased risk of colorectal cancer (CRC), but causal relationship has not yet been confirmed. We investigate the direction of causation between vitamin D and CRC by extending the conventional approaches to allow pleiotropic relationships and by explicitly modelling unmeasured confounders.
Methods Plasma 25-hydroxyvitamin D (25-OHD), genetic variants associated with 25-OHD and CRC, and other relevant information was available for 2645 individuals (1057 CRC cases and 1588 controls) and included in the model. We investigate whether 25-OHD is likely to be causally associated with CRC, or vice versa, by selecting the best modelling hypothesis according to Bayesian predictive scores. We examine consistency for a range of prior assumptions.
Results Model comparison showed preference for the causal association between low 25-OHD and CRC over the reverse causal hypothesis. This was confirmed for posterior mean deviances obtained for both models (11.5 natural log units in favour of the causal model), and also for deviance information criteria (DIC) computed for a range of prior distributions. Overall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores.
Conclusion Results suggest causal association between 25-OHD and colorectal cancer, and support the need for randomised clinical trials for further confirmations.
Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer
Chao Ren (firstname.lastname@example.org), Miao-zhen Qiu (email@example.com), De-shen Wang (firstname.lastname@example.org), Hui-yan Luo (email@example.com) Dong-sheng Zhang (firstname.lastname@example.org), Zhi-qiang Wang (email@example.com) Feng-hua Wang (firstname.lastname@example.org), Yu-hong Li (email@example.com) Zhi-wei Zhou (firstname.lastname@example.org), Rui-hua Xu (email@example.com)
Abstract Background Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown.
Methods 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D.
Results The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68nmol/L, among whom 114(57.9%) were deficient in Vitamin D(<50nmol/L), 67(34%) were insufficient (50-75nmol/L) and 16(8.1%) were sufficient (>75nmol/L). Clinical stage (P = 0.004) and lymph node metastasis classification (P = 0.009) were inversely associated with vitamin D levels.
The patients with high vitamin D levels group (≥50nmol/L) had a higher overall survival compared with the low vitamin D levels group (<50nmol/L)(P = 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (P = 0.019).
Conclusions Vitamin D deficiency may be associated with poor prognosis in gastric cancer.
Source : Journal of Translational Medicine 2012, 10:16 doi:10.1186/1479-5876-10-16 Link to Full Article
Calcitriol in cancer treatment: From the lab to the clinic Tomasz M. Beer and Anne Myrthue
Abstract 1,25-Dihydroxyvitamin D (calcitriol), the most active metabolite of vitamin D, has significant antineoplastic activity in preclinical models. Several mechanisms of activity have been proposed. These include inhibition of proliferation associated with cell cycle arrest and, in some models, differentiation, reduction in invasiveness and angiogenesis, and induction of apoptosis. Proposed mechanisms differ between tumor models and experimental conditions, and no unifying hypothesis about the mechanism of antineoplastic activity has emerged. Synergistic and/or additive effects with cytotoxic chemotherapy, radiation, and other cancer drugs have been reported. Significantly supraphysiological concentrations of calcitriol are required for antineoplastic effects. Such concentrations are not achievable in patients when calcitriol is dosed daily due to predictable hypercalcemia and hypercalcuria; however, phase I trials have demonstrated that intermittent dosing allows substantial dose escalation and has produced potentially therapeutic peak calcitriol concentrations. Recently, a phase II study reported encouraging levels of activity for the combination of high-dose calcitriol and docetaxel administered on a weekly schedule in patients with androgen-independent prostate cancer. This regimen is now under study in a placebo-controlled randomized trial in androgen-independent prostate cancer and in phase II studies in several other tumor types. Further work is needed to elucidate the molecular mechanisms of antineoplastic activity and optimal clinical applications of calcitriol in cancer.
Conclusions Calcitriol exerts potent antineoplastic activity in a broad range of tumor models. Several mechanisms of activity have been proposed. Growth inhibition and accumulation in G0-G1, associated with transcriptional activation of CDK inhibitors p27Kip1 and/or p21Waf1 has been the most extensively studied mechanism; however, effects on other mitogenic signals, induction of apoptosis, and inhibition of invasiveness and angiogenesis have also been reported.Additive and/or synergistic activity has been reported with cytotoxic chemotherapy, radiation, and other cancer drugs. At present, no unifying hypothesis for calcitriol's anticancer effects has been formulated. Indeed, it is likely that different mechanisms predominate in different neoplasms.The translation of these preclinical finding into patient care had been hampered by predictable hypercalcemia and hypercalcuria when calcitriol is dosed daily. Calcitriol concentrations that, based on preclinical data, are thought to be necessary for antineoplastic activity, are not achievable with conventional daily dosing. In contrast, intermittent administration of calcitriol has allowed substantial dose escalation. This approach has moved forward in clinical trials. Recently, a phase II study reported encouraging levels of activity for the combination of high-dose calcitriol and docetaxel administered on a weekly schedule in patients with AIPC. This regimen is now under study in a placebo-controlled randomized trial. Further work is needed to fully understand the molecular mechanisms of activity and optimal clinical applications of calcitriol in cancer.
Vitamin D and calcium supplementation reduces cancer risk:results of a randomized trial1,2
Joan M Lappe, Dianne Travers-Gustafson, K Michael Davies, Robert R Recker, and Robert P Heaney
ABSTRACT Background: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking.
Objective: The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types.
Design: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged55 y in a 9-county rural area of Nebraska centered at latitude 41.4°N. Subjects were randomly assigned to receive 1400– 1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca D), or placebo.
Results: When analyzed by intention to treat, cancer incidence was lower in the CaDwomen than in the placebo control subjects (P 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the CaDand Ca-only groups were 0.402 (P0.01) and 0.532 (P0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca D group fell to 0.232 (CI: 0.09, 0.60; P 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk.
Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women.
This trial was registered at clinicaltrials.gov as NCT00352170. Am J Clin Nutr 2007;85:1586–91
Serum 25-Hydroxyvitamin D3 Levels Are Associated With Breslow Thickness at Presentation and Survival From Melanoma
Julia A. Newton-Bishop,* Samantha Beswick, Juliette Randerson-Moor, Yu-Mei Chang, Paul Affleck, Faye Elliott, May Chan, Susan Leake, Birute Karpavicius, Sue Haynes, Kairen Kukalizch, Linda Whitaker, Sharon Jackson, Edwina Gerry, Clarissa Nolan, Chandra Bertram, Jerry Marsden, David E. Elder, Jennifer H. Barrett, and D. Timothy Bishop
From the Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds; Department of Dermatology, University Hospital Birmingham National Health Service Foundation Trust, Birmingham, United Kingdom; and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA.
Purpose: A cohort study was carried out to test the hypothesis that higher vitamin D levels reduce the risk of relapse from melanoma.
Methods: A pilot retrospective study of 271 patients with melanoma suggested that vitamin D may protect against recurrence of melanoma. We tested these findings in a survival analysis in a cohort of 872 patients recruited to the Leeds Melanoma Cohort (median follow-up, 4.7 years).
Results: In the retrospective study, self-reports of taking vitamin D supplements were nonsignificantly correlated with a reduced risk of melanoma relapse (odds ratio= 0.6; 95% CI, 0.4 to 1.1; P = .09). Nonrelapsers had highermean 25-hydroxyvitamin D3 levels than relapsers (49 v 46 nmol/L;P = .3; not statistically significant). In the cohort (prospective)study, higher 25-hydroxyvitamin D3 levels were associated withlower Breslow thickness at diagnosis (P = .002) and were independently protective of relapse and death: the hazard ratio for relapse-freesurvival (RFS) was 0.79 (95% CI, 0.64 to 0.96; P = .01) fora 20 nmol/L increase in serum level. There was evidence of interaction between the vitamin D receptor (VDR) BsmI genotype and serum25-hydroxyvitamin D3 levels on RFS.
Conclusion: Results from the retrospective study were consistent with a role for vitamin D in melanoma outcome. The cohort study tests this hypothesis,providing evidence that higher 25-hydroxyvitamin D3 levels,at diagnosis, are associated with both thinner tumors and better survival from melanoma, independent of Breslow thickness. Patients with melanoma, and those at high risk of melanoma, should seek to ensure vitamin D sufficiency. Additional studies are needed to establish optimal serum levels for patients with melanoma.
NOTE The body makes vitamin D when exposed to the ultraviolet B (UVB) rays in sunlight. You probably need from 5 to 30 minutes of exposure to the skin on your face, arms, back or legs twice every week. Sources of Vitamin D - Cod Liver Oil 1 tblspn, Fish (salmon being the highest), Milk + Margarine (Vitamin D fortified), Eggs (yolk contains Vit D), Cereals (Vit D fortified), Liver and Beef, Cheese