Vitamin D, Calcium, and Colorectal Neoplasia: New Insights on Mechanisms of Action

Jacobs, Elizabeth T.; Jurutka, Peter W.; Martı́nez, Marı́a Elena; Alberts, David S.

doi:10.1158/1940-6207.capr-09-0019

Cited by 12 publications

(10 citation statements)

References 23 publications

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“…Low calcium diets have been linked to enhanced cyclin D1 and Bcl-2 expression and decreased Bax expression, suggesting the modulation of cell cycle and apoptosis to play a part in increased tumourigenesis [2]. Dietary calcium may affect gastrointestinal malignancy directly via activation of calcium-sensing receptor (CaR) and binding of bile acids in gastrointestinal tract, and indirectly by increasing serum calcium levels [1,22]. A dual effect of luminal calcium on colon cells have been observed, where it promotes differentiation and apoptosis of normal colon cells progenitor, but becomes ineffective or even tumor-promoting in carcinogenesis [23].…”

Section: Discussionmentioning

confidence: 99%

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Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study

et al. 2013

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BackgroundObservational studies have indicated that high calcium intake may prevent colorectal cancer, but as for randomized trials the results are inconclusive. Meanwhile, limited data on the link between serum calcium and cancer risk is available. We investigated the relation between serum calcium and risk of different gastrointestinal cancers in a prospective study.MethodsA cohort based on 492,044 subjects with baseline information on calcium (mmol/L) and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse associations between standardised levels, quartiles and age/sex-specific categories of serum calcium and risk of oesophageal, stomach, colon, rectal cancer and also colorectal cancer combined, while taking into account serum albumin and other comorbidities.ResultsDuring 12 years of follow-up, we identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon cancers, and 1495 rectal cancers. A positive association was found between albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 – 11.19) for high compared to normal age-specific calcium levels] and colon cancer [e.g. HR: 1.07 (95% CI: 1.00 – 1.14) for every SD increase of calcium] as well as colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of calcium] in women. In men there were similar but weaker non-statistically significant trends.ConclusionThe positive relation between serum calcium, oesophageal cancer and colorectal cancer calls for further studies including calcium regulators to evaluate whether there is a true link between calcium metabolism and development of gastrointestinal cancer.

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Section: Discussionmentioning

confidence: 99%

“…On the other hand, how exactly serum calcium influences carcinogenesis remains indefinite. It is suggested that the rise of extracellular calcium results in increased cytosolic levels of calcium, which subsequently affects multiple cellular processes including cell cycle and apoptosis, possibly via Ras and β-catenin pathways [22,24]. …”

Section: Discussionmentioning

confidence: 99%

Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study

et al. 2013

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“…In a trial by Lappe et al (60), there was a statistically significant reduction in overall cancer risk and fewer breast cancer cases among women receiving 1400–1500 mg of calcium plus 1100 IU of vitamin D per day compared to placebo(60). While the number of incident breast cancer cases in the trial was low and these results must be interpreted with caution, they may indicate that supplementation with vitamin D at doses higher than that used in the WHI trial may be required for prevention of breast cancer (61). Nonetheless the possibility remains that the impact of both endogenous synthesis and intake of vitamin Don circulating 25(OH)D concentrations is regulated by homeostatic mechanisms that cannot, or perhaps should not, be over-ridden by high-dose supplementation.…”

Section: Does Vitamin D Have a Mechanism Of Action Or Is It A Biomarkmentioning

confidence: 97%

Vitamin D: Marker or Mechanism of Action?

Jacobs

Martı́nez

Jurutka³

2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The field of vitamin D and cancer research has been moving forward quickly. However, some challenges remain regarding the interpretation and integration of data collected from epidemiological investigations and laboratory experiments. These include consideration of vitamin D biology, a better understanding of characteristics that affect concentrations of the biomarker of vitamin D status, 25(OH)D, and elucidation of variation in response to vitamin D supplementation. To further the field of vitamin D and cancer prevention, future studies will need to bridge the gap between the epidemiology and molecular biology of vitamin D activity in carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(4); 585-90. Ó2011 AACR.

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“…In comparison, Figure 3b shows the effect of a modified chemopreventive regimen where ASP and FA were encapsulated in PLGA 50:50 polymer NPs (20) and mixed with free Ca and administered to rats in Set 2 (G13–G15). When compared to the AOM treated group (G9), significant differences were observed wherein treatment with the modified form of G13 (360 mg/kg) showed a significant inhibition of ACFs in the distal colon by approximately 75%.…”

Section: Resultsmentioning

confidence: 99%

“…Prior studies have suggested an inverse association between Ca intake and the occurrence of colorectal neoplasia (19). A mechanism by which it affects the intestinal epithelium is through activation of a Ca-sensing receptor with resultant growth inhibition and differentiation of transformed cells (20, 21). Due to the abundant availability of Ca, low cost and its potential effectiveness in preventing CRC, Ca is a good candidate for further studies in chemoprevention.…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention of Colon Cancer in a Rat Carcinogenesis Model Using a Novel Nanotechnology-Based Combined Treatment System

Chaudhary

Sutaria²,

Huang³

et al. 2011

Cancer Prevention Research

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Colorectal cancer (CRC) is the third most common cause of cancer death in the US, accounting for ~51,000 deaths each year. We have previously shown in vitro chemopreventive effects of mixtures of aspirin, folic acid and calcium (AFAC) on colon cancer cell lines. The objective of the present study was to evaluate the in vivo effects of orally administered, colon targeted chemopreventive combination regimens on the inhibition of aberrant crypt foci (ACF) in a rat model of colon carcinogenesis using (1) unmodified (free drug) combinations of AFAC, and (2) nanoparticle-encapsulated combinations of the same agents. A 14-week animal study was conducted in three phases to determine an optimal effective dose from AFAC combinations and evaluate the efficacy of nanotechnology-based chemopreventive regimens administered in combined (mixtures), and individual (single entity) forms. ACF inhibition when compared to azoxymethane (AOM)-treated rat control group was significant in both, the unmodified and the modified nanoparticle-mediated chemopreventive regimens, demonstrating a range of 31 – 38% (p < 0.05) and 50 – 75% (p < 0.001) reduction respectively, in the number of ACFs. In addition, the nanoparticulate combination regimens of AFAC demonstrated a 2-fold increase in suppression of ACF compared to free drug mixtures. Individual administration of nanoparticle encapsulated drugs showed no significant effect on the reduction of ACF. Histochemical analysis provided further confirmation of chemopreventive effects, demonstrating a significant reduction in cell nuclear proliferation. Overall, our results provide a strong proof-of-concept using nanoparticle-mediated combination treatment in the chemoprevention of colon cancer.

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Vitamin D, Calcium, and Colorectal Neoplasia: New Insights on Mechanisms of Action

Cited by 12 publications

References 23 publications

Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study

Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study

Vitamin D: Marker or Mechanism of Action?

Chemoprevention of Colon Cancer in a Rat Carcinogenesis Model Using a Novel Nanotechnology-Based Combined Treatment System

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