Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ et al.. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer 128, 1414-1424

European Institute of Oncology, Milano, Italy.
International Journal of Cancer (Impact Factor: 5.09). 03/2011; 128(6):1414-24. DOI: 10.1002/ijc.25439
Source: PubMed


Epidemiological studies have suggested a reduced risk of several cancers associated with high vitamin D status. We performed a systematic review with meta-analyses of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer and colonic adenoma. The literature of December 2009 was searched without language restriction. The meta-regression analysis was done to compute dose-response effects. Because in case-control studies, serum 25-hydroxyvitamin D level is measured after the diagnosis of cancer, separate analyses for case-control and prospective studies were done. We identified 35 independent studies. The seven studies on colorectal adenomas were heterogeneous in terms of endpoint and control for major confounding factors, and we did not perform a meta-analysis of these data. The summary relative risk (SRR) and (95% confidence interval) for a 10 ng/ml increase in serum 25-hydroxyvitamin D was 0.85 (0.79; 0.91) for colorectal cancer (2,630 cases in 9 studies); 0.89 (0.81;0.98) for breast cancer (6,175 cases in 10 studies); and 0.99 (0.95;1.03) for prostate cancer (3,956 cases in 11 studies). For breast cancer, case-control studies (3,030 cases) had major limitations and obtained SRR of 0.83 (0.79; 0.87) whereas SRR of prospective studies (3,145 cases) was 0.97 (0.92; 1.03). For colorectal and breast cancer, differences between cases and controls in the season of blood draw or in overweight/obesity or physical inactivity could not explain the results. In conclusion, a consistent inverse relationship between serum 25-hydroxyvitamin D levels and colorectal cancer was found. No association was found for breast and prostate cancer.

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    • "However these are observational studies that cannot give definitive answers to question if low vitamin D status is a causal factor for increased risk of cancer, or simply an indicator of poor health status. To assess if there is a causal link, good randomized clinical trials that verify the impact of vitamin D supplementation on cancer incidence need to be performed [52] [53]. "
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    ABSTRACT: The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ("moderate", "high" and "very high confidence") according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7% reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least "high confidence" studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with "high confidence". When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin. Copyright © 2014 Elsevier B.V. All rights reserved.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2014; 769. DOI:10.1016/j.mrfmmm.2014.06.001 · 3.68 Impact Factor
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    • "Severe Vitamin D3 deficiency, measured by serum 25-hydroxyvitamin D levels, or deletion of the VDR gene is associated with increased cancer risk [2], [3]. Although topical application of 1,25(OH)2D3 reduced UVB-induced tumor burden in the SKH-1 mouse model of squamous cell carcinoma [4], protective effects of dietary Vitamin D3 against the development of skin cancer has not been examined. "
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    ABSTRACT: ΔNp63α, a proto-oncogene, is up-regulated in non-melanoma skin cancers and directly regulates the expression of both Vitamin D receptor (VDR) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). Since ΔNp63α has been shown to inhibit cell invasion via regulation of VDR, we wanted to determine whether dietary Vitamin D3 protected against UVB induced tumor formation in SKH-1 mice, a model for squamous cell carcinoma development. We examined whether there was a correlation between dietary Vitamin D3 and ΔNp63α, VDR or PTEN expression in vivo in SKH-1 mice chronically exposed to UVB radiation and fed chow containing increasing concentrations of dietary Vitamin D3. Although we observed differential effects of the Vitamin D3 diet on ΔNp63α and VDR expression in chronically irradiated normal mouse skin as well as UVB induced tumors, Vitamin D3 had little effect on PTEN expression in vivo. While low-grade papillomas in mice exposed to UV and fed normal chow displayed increased levels of ΔNp63α, expression of both ΔNp63α and VDR was reduced in invasive tumors. Interestingly, in mice fed high Vitamin D3 chow, elevated levels of ΔNp63α were observed in both local and invasive tumors but not in normal skin suggesting that oral supplementation with Vitamin D3 may increase the proliferative potential of skin tumors by increasing ΔNp63α levels.
    PLoS ONE 09/2014; 9(9):e107052. DOI:10.1371/journal.pone.0107052 · 3.23 Impact Factor
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    • "Reduced serum levels of 25(OH)D have been reported correlated with several detrimental health effects [5] [6] [7] [8], including worst prognosis of some cancers [9] [10]. A meta-analysis of 35 independent case-control and cohort studies investigating the association of serum 25(OH)D levels with cancer showed a consistent inverse relationship between circulating 25(OH)D levels and colorectal cancer risk [11]; no similar conclusions could however be drawn for other cancer sites. Notably, so far none of the randomised, controlled trials has shown that vitamin D supplementation can prevent cancer [12] [13] although the increase in vitamin D serum levels achieved in one of these trials, the Women's Health Initiative study, was probably insufficient [14]. "
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    ABSTRACT: Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60-3.53) and 1.64 (95% CI 1.02-2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63-1.13) for CM and 1.03 (95% CI 0.95-1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.
    European journal of cancer (Oxford, England: 1990) 07/2014; 50(15). DOI:10.1016/j.ejca.2014.06.024 · 5.42 Impact Factor
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