scholarly journals The association between circulating levels of vitamin D and inflammatory markers in the first 2 years after colorectal cancer diagnosis

2020 ◽  
Vol 13 ◽  
pp. 175628482092392 ◽  
Author(s):  
Evertine Wesselink ◽  
Michiel Balvers ◽  
Martijn J. L. Bours ◽  
Johannes H. W. de Wilt ◽  
Renger F. Witkamp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Progression ◽  
Inflammatory Markers ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Active Form ◽  
Inverse Association ◽  
Z Score ◽  
Regression Analyses

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (β −0.06, 95% CI −0.08 to −0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (β −0.17, 95% CI −0.25 to −0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

scholarly journals Antineoplastic effects of 1,25(OH)2D3 and its analogs in breast, prostate and colorectal cancer

2013 ◽  
Vol 20 (2) ◽  
pp. R31-R47 ◽  
Author(s):  
Carlien Leyssens ◽  
Lieve Verlinden ◽  
Annemieke Verstuyf
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Side Effects ◽  
Active Form ◽  
Malignant Cell ◽  
Inverse Association ◽  
Dihydroxyvitamin D ◽  
Cancer Types ◽  
Epidemiological Link

The active form of vitamin D3, 1,25-dihydroxyvitamin D3(1,25(OH)2D3), is mostly known for its importance in the maintenance of calcium and phosphate homeostasis. However, next to its classical effects on bone, kidney and intestine, 1,25(OH)2D3also exerts antineoplastic effects on various types of cancer. The use of 1,25(OH)2D3itself as treatment against neoplasia is hampered by its calcemic side effects. Therefore, 1,25(OH)2D3-derived analogs were developed that are characterized by lower calcemic side effects and stronger antineoplastic effects. This review mainly focuses on the role of 1,25(OH)2D3in breast, prostate and colorectal cancer (CRC) and the underlying signaling pathways. 1,25(OH)2D3and its analogs inhibit proliferation, angiogenesis, migration/invasion and induce differentiation and apoptosis in malignant cell lines. Moreover, prostaglandin synthesis and Wnt/b-catenin signaling are also influenced by 1,25(OH)2D3and its analogs. Human studies indicate an inverse association between serum 25(OH)D3values and the incidence of certain cancer types. Given the literature, it appears that the epidemiological link between vitamin D3and cancer is the strongest for CRC, however more intervention studies and randomized placebo-controlled trials are needed to unravel the beneficial dose of 1,25(OH)2D3and its analogs to induce antineoplastic effects.

scholarly journals VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaojun Zhu ◽  
Zihuan Wang ◽  
Jianqun Cai ◽  
Chunqiu Pan ◽  
Simin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Progression ◽  
Active Form ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Lower Survival Rate ◽  
Migration Capacity

Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.

scholarly journals Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vidya Lakshmi Purushothaman ◽  
Raphael E. Cuomo ◽  
Cedric F. Garland ◽  
Timothy K. Mackey
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Age Groups ◽  
Incidence Rates ◽  
Ultraviolet B ◽  
Inverse Association ◽  
Crude Incidence ◽  
Age Dependent ◽  
Uvb Exposure

Abstract Background Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

scholarly journals The Chalcone Lonchocarpin Inhibits Wnt/β-Catenin Signaling and Suppresses Colorectal Cancer Proliferation

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1968 ◽  
Author(s):  
Danilo Predes ◽  
Luiz F. S. Oliveira ◽  
Laís S. S. Ferreira ◽  
Lorena A. Maia ◽  
João M. A. Delou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Active Form ◽  
Colorectal Cancer Cell ◽  
Intestinal Cell ◽  
Transcriptional Level ◽  
Mice Model

The deregulation of the Wnt/β-catenin signaling pathway is a central event in colorectal cancer progression, thus a promising target for drug development. Many natural compounds, such as flavonoids, have been described as Wnt/β-catenin inhibitors and consequently modulate important biological processes like inflammation, redox balance, cancer promotion and progress, as well as cancer cell death. In this context, we identified the chalcone lonchocarpin isolated from Lonchocarpus sericeus as a Wnt/β-catenin pathway inhibitor, both in vitro and in vivo. Lonchocarpin impairs β-catenin nuclear localization and also inhibits the constitutively active form of TCF4, dnTCF4-VP16. Xenopus laevis embryology assays suggest that lonchocarpin acts at the transcriptional level. Additionally, we described lonchocarpin inhibitory effects on cell migration and cell proliferation on HCT116, SW480, and DLD-1 colorectal cancer cell lines, without any detectable effects on the non-tumoral intestinal cell line IEC-6. Moreover, lonchocarpin reduces tumor proliferation on the colorectal cancer AOM/DSS mice model. Taken together, our results support lonchocarpin as a novel Wnt/β-catenin inhibitor compound that impairs colorectal cancer cell growth in vitro and in vivo.

scholarly journals Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

2015 ◽  
Vol 24 (12) ◽  
pp. 1820-1828 ◽  
Author(s):  
A. Suzanne van Harten-Gerritsen ◽  
Michiel G.J. Balvers ◽  
Renger F. Witkamp ◽  
Ellen Kampman ◽  
Fränzel J.B. van Duijnhoven
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Progression ◽  
Epidemiological Studies ◽  
Mechanistic Studies ◽  
Future Directions ◽  
Colorectal Cancer Progression

scholarly journals Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

2020 ◽  
Author(s):  
Vidya Lakshmi Purushothaman ◽  
Raphael E Cuomo ◽  
Cedric F Garland ◽  
Tim Ken Mackey
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Age Groups ◽  
Incidence Rates ◽  
Ultraviolet B ◽  
Inverse Association ◽  
Crude Incidence ◽  
Age Dependent ◽  
Uvb Exposure

Abstract Background: Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally.Methods: In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps.Results: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates.Conclusion: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

scholarly journals Vitamin D Enhances Radiosensitivity of Colorectal Cancer by Reversing Epithelial-Mesenchymal Transition

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyue Yu ◽  
Qian Wang ◽  
Baocai Liu ◽  
Ning Zhang ◽  
Guanghui Cheng
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Epithelial Mesenchymal Transition ◽  
Active Form ◽  
Plasminogen Activator Inhibitor ◽  
Biologically Active ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mesenchymal Transition

Colorectal cancer (CRC) is often resistant to conventional therapies. Previous studies have reported the anticancer effects of vitamin D in several cancers, its role in radiotherapy (RT) remains unknown. We found that 1α, 25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, had antitumor effect on CRC and sensitized CRC cells to ionizing radiation (IR). VD3 demonstrated synergistic effect in combination with IR, which were detected by colony formation and cell proliferation assay. Radiosensitivity restoration induced by VD3 was associated with a series of phenotypes, including apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). Using proteomics, “regulation of cell migration” and “cadherin” were found to be obviously enriched GO terms. Moreover, cystatin D and plasminogen activator inhibitor-1 (PAI-1), the differentially expressed proteins, were associated with EMT. Next, we confirmed the contributions of these two genes in enhancing IR sensitivity of CRC cells upon inhibition of EMT. As determined by proteomics, the mechanism underlying such sensitivity involved partially block of JAK/STAT3 signaling pathway. Furthermore, VD3 also elicited sensitization to RT in xenograft CRC models without additional toxicity. Our study revealed that VD3 was able to act in synergy with IR both in vitro and in vivo and could also confer radiosensitivity by regulating EMT, thereby providing a novel insight for elevating the efficacy of therapeutic regimens.

scholarly journals Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality

2020 ◽  
Vol 111 (5) ◽  
pp. 1007-1017
Author(s):  
Evertine Wesselink ◽  
Dieuwertje E Kok ◽  
Martijn J L Bours ◽  
Johannes H W de Wilt ◽  
Harm van Baar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Calcium Intake ◽  
Cancer Recurrence ◽  
Underlying Mechanism ◽  
Inverse Association ◽  
Vitamin D Metabolism ◽  
Magnesium Intake ◽  
All Cause Mortality ◽  
Sufficient Vitamin

ABSTRACT Background Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism. Objectives We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality. Methods The study population included 1169 newly diagnosed stage I–III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another. Results Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed. Conclusions Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.

Higher intakes of dietary vitamin D, calcium and dairy products are inversely associated with the risk of colorectal cancer: a case–control study in China

2019 ◽  
Vol 123 (6) ◽  
pp. 699-711 ◽  
Author(s):  
Xin Zhang ◽  
Yu-Jing Fang ◽  
Xiao-Li Feng ◽  
Alinuer Abulimiti ◽  
Chu-Yi Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Risk ◽  
Dairy Products ◽  
Dairy Product ◽  
Colorectal Cancer Risk ◽  
Dietary Vitamin ◽  
Cancer Site ◽  
Inverse Association ◽  
Dietary Vitamin D

AbstractThe effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial. The present study investigated the association between these dietary intakes and the risk of colorectal cancer in Guangdong, China. From July 2010 to December 2018, 2380 patients with colorectal cancer and 2389 sex- and age-matched controls were recruited. Dietary intake data were collected through face-to-face interviews using a validated FFQ. Unconditional multivariable logistic regression models were used to calculate the OR and 95 % CI after adjusting for various confounders. Higher dietary vitamin D and Ca intakes were associated with 43 and 52 % reductions in colorectal cancer risk, with OR of 0·57 (95 % CI 0·46, 0·70) and 0·48 (95 % CI 0·39, 0·61), respectively, for the highest quartile (v. the lowest quartile) intakes. A statistically significant inverse association was observed between total dairy product intake and colorectal cancer risk, with an adjusted OR of 0·32 (95 % CI 0·27, 0·39) for the highest v. the lowest tertile. Subjects who drank milk had a 48 % lower risk of colorectal cancer than those who did not (OR 0·52, 95 % CI 0·45, 0·59). The inverse associations of dietary vitamin D, Ca, total dairy products and milk intakes with the risk of colorectal cancer were independent of sex and cancer site. Our study supports the protective effects of high dietary vitamin D, Ca and dairy products intakes against colorectal cancer in a Chinese population.

Sign in / Sign up

Export Citation Format

Share Document