UMLS:C0699790 - FACTA Search

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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association.
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PMID:Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer. 1642 62

Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving increased attention lately for its role in maintaining optimal health. Although the calcemic effects of vitamin D have been known for about a century, the non-calcemic effects have been studied intently only during the past two-three decades. The strongest links to the beneficial roles of UVB and vitamin D to date are for bone and muscle conditions and diseases. There is also a preponderance of evidence from a variety of studies that vitamin D reduces the risk of colon cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33 ng/mL (82 nmol/L) associated with a 50% lower incidence of colorectal cancer. There is also reasonable evidence that vitamin D reduces the risk of breast, lung, ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker, primarily ecologic, evidence for the role of vitamin D in reducing the risk of an additional dozen types of cancer. There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts its effect are generally well understood for the various conditions and diseases discussed here.
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PMID:Epidemiology of disease risks in relation to vitamin D insufficiency. 1654 42

The anti-cancer activity of calcitriol, the active metabolite of Vitamin D, in the colon is usually attributed to its anti-proliferative and pro-differentiative actions. The levels of reactive oxygen species (ROS) are high in colon carcinomas due to increased aerobic metabolism and exposure to various anti-cancer modalities. We examined whether calcitriol modulates the response of colon cancer cells to the cytotoxic action of the common mediator of ROS injury, H2O2. Pretreatment with calcitriol (100 nM, 48 h) sensitized HT-29 colon cancer cells to cell death induced by acute exposure to H2O2 or chronic exposure to the H2O2 generating system, glucose/glucose-oxidase. Although the morphological features of H2O2-induced HT-29 cell death are consistent with apoptosis, we detected no executioner caspase activation in response to cytotoxic concentrations of H2O2 and treatment with a pan-caspase inhibitor did not affect H2O2-induced cytotoxicity nor its enhancement by calcitriol. Conversely, exposure of HT-29 cells to sub-toxic concentrations of H2O2 resulted in low executioner caspase activation that was inhibited by pretreatment with calcitriol. The sensitization of colon cancer cells to ROS-induced cytotoxicity may contribute to its assumed action as a chemopreventive agent and to its therapeutic potential alone or in combination with other anti-cancer modalities.
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PMID:Calcitriol sensitizes colon cancer cells to H2O2-induced cytotoxicity while inhibiting caspase activation. 1688 57

Vitamin D(3) metabolites and analogues have recently been shown to play an important role in the regulation of a number of important cellular processes, including proliferation, differentiation, and apoptosis, in addition to their established roles in mineral homeostasis. The actions of these secosteroids involve both rapid, nongenomic effects and genomic effects; the latter mediated via the vitamin D receptor and other transcription factors. Their effects have been described in a variety of cell types, including normal and malignant colonocytes. This article summarizes the rapid and genomic actions of vitamin D(3) metabolites and analogues on normal and pathologic processes in the colon, with particular emphasis on the potential of these secosteroids to prevent colon cancer.
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PMID:The role of vitamin D in normal and pathologic processes in the colon. 1703 Nov 54

Vitamin D derivatives can modulate proliferation and differentiation of cancer cells. Our main source of Vitamin D is ultraviolet (UV) radiation-induced synthesis in skin following sun exposure. UV measurements show that the ambient annual UV exposures increase by about 50% from north to south in Norway. As judged from the incidence rates of squamous cell carcinoma, the same is true for the average personal UV exposures. Solar ultraviolet B (UVB) (280-320nm) exhibits a strong seasonal variation with a minimum during the winter months. The present work aims at investigating the impact of season of diagnosis and residential region, both influencing the Vitamin D level, on the risk of death from lung cancer in patients diagnosed in Norway. Data on all incident cases of lung cancer between 1964 and 2000 were collected. Risk estimates were calculated as relative risk (RR), with 95% confidence intervals using Cox regression model. The seasonal variation of 25-hydroxyvitamin D was assessed from routine measurements of 15,616 samples performed at The Hormone Laboratory of Aker University Hospital. Our results indicate that season of diagnosis is of prognostic value for lung cancer patients, with a approximately 15% lower case fatality for young male patients diagnosed during autumn versus winter (RR=0.85; 95% CI, -0.73 to 0.99; p=0.04). Residing in a high UV region resulted in a further lowering of the death risk than residing in a low UV region. We propose, in agreement with earlier findings for prostate-, breast- colon cancer and Hodgkins lymphoma, that a high level of sun-induced 25-hydroxyvitamin D can be a prognostic advantage for certain groups of lung cancer patients, notably for young men. Lung cancer has for several decades been the leading cause of cancer-related mortality in men in Norway and during the last two decades, became the second most common cause of cancer-related death in women . There are two main types of lung cancer: small cell lung cancer for which chemotherapy is the primary treatment and non-small cell lung cancer, which in its early stages is treated primarily with surgery. Gender-related differences have been described in the literature with respect to survival after therapy, male gender being a significant independent negative prognostic factor . In Norway the 5 years relative survival for localized tumours is about 30% for females and 20% for males. Calcitriol, which is the most active form of Vitamin D, is involved in key regulatory processes such as proliferation, differentiation and apoptosis in a wide variety of cells . Mechanisms for these actions have been proposed to be the interaction of active Vitamin D derivatives with a specific nuclear receptor (VDR receptor) and/or with membrane targets . In vitro studies, performed with lung cancer cell lines, have shown an inhibitive effect of Vitamin D derivatives on cell-growth and proliferation . Furthermore, animal studies have demonstrated the capability of these compounds to suppress invasion, metastasis and angiogenesis in vivo , suggesting that administration of Vitamin D derivatives may be used as adjuvant therapy for lung cancer. Humans get optimal Vitamin D levels by exposure to sun or artificial ultraviolet B (UVB, 280-320nm) sources , and possibly also by consumption of food rich in this nutrient (fat fish, eggs, margarine, etc.) or of vitamin supplements . Among these sources, solar radiation appears to be the most important one . Thus, the Vitamin D status (assessed by the serum levels of 25-hydroxyvitamin D, calcidiol) exhibits a strong seasonal variation that parallels the seasonal change in the fluence of solar UVB that reaches the ground. During winter, the UVB fluence rate in the Nordic countries (50-71 degrees N) is below the level required for Vitamin D synthesis in skin . The maximal level of calcidiol is reached between the months July and September, and is 20-120% higher than the corresponding winter level . Recently we hypothesised that the seasonal variation of calcidiol might be of prognostic significance for colon-, breast- prostate cancer as well as for Hodgkins lymphoma in Norway. Patients diagnosed during summer and autumn have a better survival after standard treatment than patients diagnosed during the winter season . This might be a consequence of a higher Vitamin D level. An American study investigated the effect of season of surgery and recent Vitamin D intake on the survival of non-small cell lung cancer patients. The authors reported a significant beneficial joint effect of summer season and high Vitamin D intake compared with winter season and low Vitamin D intake while Vitamin D intake alone did not affect prognosis. Similar results were recently reported from a large study in United Kingdom involving over a million cancer patients including over 190,000 patients diagnosed with lung cancer . Norway (58-71 degrees N) has a significant north-south variation in UV fluence. This makes the country suitable for studies relating cancer epidemiology to UV levels . We investigated whether variations in UV, and, consequently, in Vitamin D level, influence the prognosis of lung cancer, using season of diagnosis and residential regions as variables. Survival data obtained for patients diagnosed over a 40 years period were compared with variations in serum Vitamin D levels obtained from routine measurements performed in The Hormone Laboratory of Aker University Hospital during the period 1996-2001. Seasonal and gender variations in Vitamin D level have been estimated from the analyses.
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PMID:Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role? 1720 91

In vivo and in vitro studies suggest that dairy products, calcium, and dietary vitamin D inhibits the development of colorectal cancer (CRC). A meta-analysis was performed to evaluate this relationship in observational studies. Data from 60 epidemiological studies enrolling 26,335 CRC cases were pooled using a general variance-based meta-analytic method. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated for the highest vs. the lowest intake categories. Sensitivity analyses tested the robustness of these summary effect measures and the statistical heterogeneity. The summary RR for high milk and dairy product intake, respectively, on colon cancer risk was 0.78 (95% CI = 0.67-0.92) and 0.84 (95% CI = 0.75-0.95). Milk intake was unrelated to rectal cancer risk. High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon. The risk reduction associated with calcium was similar for dietary and supplemental sources. Vitamin D was associated with a nonsignificant 6% reduction in CRC risk. Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC. Low vitamin D intake in the study populations may limit the ability to detect a protective effect if one exists.
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PMID:Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. 1911 75

In vitro and in vivo studies have demonstrated that the biologically active vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D3, calcitriol) suppresses proliferation and induces differentiation in various cell types, including human keratinocytes and melanocytes. Vitamin D is synthesized in the skin from 7-dehydrocholesterol (7-DHC) by the action of UV-B. There are two principal enzymes involved in the formation of circulating 1,25(OH)2D3 from vitamin D, the hepatic microsomal or mitochondrial vitamin D-25-hydroxylase (CYP27A1) and the renal mitochondrial 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) for vitamin D and 25(OH)D3 (calcidiol), respectively. Extrarenal activity of CYP27B1 has been reported in various cell types including macrophages, keratinocytes, prostate and colon cancer cells. It has been speculated that the extrarenal CYP27B1-mediated local synthesis of 1,25(OH)2D3 represents a key regulator of important cellular functions including growth and differentiation in various cell types and tissues by autocrine or paracrine signalling pathways. The keratinocyte represents the only cell type where the complete enzymatic machinery for the synthesis of 1,25(OH)2D from 7-DHC is present and where the synthesis of 1,25(OH)2D3 from 7-DHC has been shown. In this study, we characterized the pattern of CYP27B1 splice variants in HaCaT keratinocytes in vitro. Applying nested touch-down PCR, the full length CYP27B1 gene product and several additional CYP27B1 splice variants were detected. The pattern of CYP27B1 splice variants varied depending on the cell density, the calcium concentration of the medium ([Ca2+]o), and UV-B treatment. It can be speculated whether increased expression of CYP27B1 splice variants that lack enzymatic activity (Hyd-V3/V5) may result in a reduction of enzymatic activity and in reduced synthesis of 1,25(OH)2D3. Further study of the impact of CYP27B1 splice variants on the vitamin D pathway in keratinocytes and other cell types is warranted.
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PMID:Expression of 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase, CYP27B1) splice variants in HaCaT keratinocytes and other skin cells: modulation by culture conditions and UV-B treatment in vitro. 1966 62

Since the 1970s, it has been well known that long-standing ulcerative colitis (UC) disposes to the development of colorectal adenocarcinoma (CRC). To date, CRC associated with UC is thought to arise along a pathway of dysplasia, however, primary factors for developing of UC-related dysplasia and cancer are unclear. Vitamin D, which works through binding the vitamin D receptor (VDR) has an important role in cancer progression and immune response. In this study, we investigated the impact of VDR expression on UC as well as colon cancer. We examined retrospectively the expression of VDR in extraction specimens of UC (n=124) patients by immunohistochemistry. We counted VDR positive cells in at least 10 fields in each case to evaluate the frequency of VDR positive cells in ductal epithelium. In addition, effect of VDR expression on inflammation was analyzed. On a normal mucosa, the expression of VDR was recognized in 58.8% of ductal cells. In UC patient, the expression of VDR was considerably decreased compared to normal mucosa, VDR positive rate was only 3.4+/-9.0%. Importantly, dysplasia and UC-CRC patients showed lower rate of VDR expression compared to non-colon cancer patients, whose expression rates were 0.6+/-1.3% and 3.8+/-10%, respectively. Moreover, long-term UC patients (more than ten years) who were at high-risk of developing CRC showed significantly lower VDR expression than short-term patients. We did not detect direct association of VDR expression with inflammation and clinical stage of UC. These findings suggested that correlation seems to exist between the level of VDR expression and carcinogenesis in UC. VDR could be a possible marker to detect dysplasia and cancer in ulcerative colitis.
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PMID:Vitamin D receptor expression is associated with colon cancer in ulcerative colitis. 1978 15

Vitamin D is associated with decreased risks of various cancers, including colon cancer. The vitamin D receptor (VDR) is a transcription factor, which plays an important role in cellular differentiation and inhibition of proliferation. A link between VDR and the RAS-mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)-AKT pathway has been suggested. However, the prognostic role of VDR expression or its relationship with PIK3CA or KRAS mutation remains uncertain. Among 619 colorectal cancers in two prospective cohort studies, 233 (38%) tumors showed VDR overexpression by immunohistochemistry. We analyzed for PIK3CA and KRAS mutations and LINE-1 methylation by Pyrosequencing, microsatellite instability (MSI), and DNA methylation (epigenetic changes) in eight CpG island methylator phenotype (CIMP)-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by MethyLight (real-time PCR). VDR overexpression was significantly associated with KRAS mutation (odds ratio, 1.55; 95% confidence interval, 1.11-2.16) and PIK3CA mutation (odds ratio, 2.17; 95% confidence interval, 1.36-3.47), both of which persisted in multivariate logistic regression analysis. VDR was not independently associated with body mass index, family history of colorectal cancer, tumor location (colon versus rectum), stage, tumor grade, signet ring cells, CIMP, MSI, LINE-1 hypomethylation, BRAF, p53, p21, beta-catenin, or cyclooxygenase-2. VDR expression was not significantly related with patient survival, prognosis, or clinical outcome. In conclusion, VDR overexpression in colorectal cancer is independently associated with PIK3CA and KRAS mutations. Our data support potential interactions between the VDR, RAS-MAPK and PI3K-AKT pathways, and possible influence by KRAS or PIK3CA mutation on therapy or chemoprevention targeting VDR.
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PMID:Vitamin D receptor expression is associated with PIK3CA and KRAS mutations in colorectal cancer. 1978 68

Non-steroidal analogs of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] represent a most particular class of analogs because they are either not directly derived from the core 1,25(OH)2D3-structure or they have modifications in the core structure that are so drastic that the steroidal structure is lost. Non-steroidal CD-ring analogs of 1,25(OH)2D3 have been developed to study the role of the central rigid CD-ring system in the biological activity of 1,25(OH)2D3. Here we review the different classes of CD-ring analogs and highlight some representative analogs such as the fluorinated D-ring analogs CD578, WU515 and WY1113 which show markedly increased differentiating activity on human SW480-ADH colon cancer cells, characterized by a stronger induction of the invasion suppressor E-cadherin and a stronger repression of the beta-catenin/TCF target oncogene c-Myc. Correspondingly, CD578, WU515 and WY1113 are more potent inhibitors of beta-catenin/TCF signaling than 1,25(OH)2D3 and induce stronger VDR-coactivator interactions. Underlying the increased biological potency of analog CD578 are additional contacts between the side chain fluorine atoms of the analog with specific residues of helix 12 (H12) of the Vitamin D Receptor (VDR) and subsequent stronger VDR-coactivator interactions.
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PMID:CD-ring modified vitamin D3 analogs and their superagonistic action. 2013 86

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