Dataset Information

Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue.

ABSTRACT: Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 106 men enrolled in the US Physicians' Health Study (PHS) diagnosed between 1983 and 2004. We also assayed for VDR protein expression among 832 men in the PHS and Health Professionals Follow-up Study cohorts. Season was characterized by date of initial tissue specimen collection categorically and by average monthly ultraviolet radiation levels. One-way analysis of variance was used to examine variation in the expression levels of six genes on the vitamin D pathway-VDR, GC, CYP27A1, CYP27B1, RXR?, CYP24A1-and VDR protein by season, adjusted for age at diagnosis and Gleason grade. Variation was also examined separately among lethal and nonlethal cases.Tumor expression levels of the six genes did not vary significantly by season of tissue collection. No consistent patterns emerged from subgroup analyses by lethal versus nonlethal cases.Unlike circulating levels of 25(OH) vitamin D, expression levels of genes on the vitamin D pathway and VDR protein did not vary overall by season of tissue collection. Epidemiological analyses of vitamin D gene expression may not be biased by seasonality.

SUBMITTER: Epstein MM

PROVIDER: S-EPMC3589913 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue.

Epstein Mara M MM Andrén Ove O Kasperzyk Julie L JL Shui Irene M IM Penney Kathryn L KL Fall Katja K Rider Jennifer R JR Stampfer Meir J MJ Andersson Swen-Olof SO Giovannucci Edward E Mucci Lorelei A LA

Cancer causes & control : CCC 20120619 8

<h4>Purpose</h4>Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.<h4>Methods</h4>Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 1 ...[more]

PMID: 22710747

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Project description:BackgroundWhile several studies have investigated the association between vitamin D deficiency and biochemical parameters, the results are still inconsistent and mostly overlook seasonal variations. This study explored the relationships between 25-hydroxy-vitamin D (25(OH)D) concentrations, biochemical markers, and seasonal variation among young males and females.MethodsA cross-sectional study was conducted among 203 individuals aged 18-24 years of both sexes residing in Brasilia, Brazil (latitude: 15°S). Sociodemographic variables, season of blood collection, and serum levels of 25(OH)D, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glycated hemoglobin (HbA1c), glucose, insulin, hs-CRP, parathyroid hormone, ionized calcium, and alkaline phosphatase were included. Descriptive statistics and differences among groups, correlations, and linear regression tests were performed.ResultsThe mean age of the participants was 21.17±1.7 years, and the mean serum 25(OH)D level was 25.76±7.0 ng/mL. Of the participants, 50.7% had vitamin D insufficiency (20 to 29.9 ng/mL), and 23.2% were vitamin D deficient (≤20 ng/mL). Vitamin D deficiency was higher in the spring (53.2%) and among females (29.5%). In young men with vitamin D insufficiency/deficiency (≤29.9 ng/mL) (n = 49), 25(OH)D levels were inversely correlated with HOMA-β (r = -0.234, p = 0.032) and triglyceride (r = -0.415, p = 0.003) levels. However, there were no significant correlations between 25(OH)D concentrations and biochemical markers among women with insufficient and deficient vitamin D levels.ConclusionThis study found a high prevalence of vitamin D insufficiency/deficiency among young individuals living in Brasília, Brazil, particularly women and during the spring season. Our findings suggest that lower 25(OH)D levels (≤29.9 ng/mL) may be associated with insulin resistance and an increased risk of cardiovascular disease in young men studied. However, further studies with larger representative samples are needed to explore the mechanisms underlying the association between vitamin D and biochemical parameters.

Project description:Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.

Dataset Information

Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue.

Publications

Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue.

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