Dataset Information

Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis.

ABSTRACT: BACKGROUND:The evidence for vitamin D reducing cancer risk is inconsistent, and it is not clear whether this reduction is related to variation in cytochrome P450 (CYP)24A1, the only enzyme known to degrade active vitamin D. We focused on evaluating the association of CYP24A1-rs2296241 polymorphism with hormone-related cancer risk by conducting a meta-analysis. METHODS:A systematic literature search was conducted in April 2014 (updated in December 2014) to identify eligible studies. A random-effects model was used to pool the odds ratio (OR). RESULTS:Eleven studies including 5,145 cases and 5,136 controls were considered for the allelic model, and eight studies of 3,959 cases and 3,560 controls were utilized for the additive, recessive, and dominant models. There was no significant association between CYP24A1-rs2296241 and hormone-related cancer risk in any of the models, yet substantial heterogeneity was observed. Subgroup analyses indicated that CYP24A1-rs2296241 variation reduced the prostate cancer risk in the additive (OR 0.91, 95% confidence interval 0.85-0.97) and recessive (OR 0.80, 95% confidence interval 0.67-0.95) models, with no evidence of heterogeneity. CONCLUSION:This meta-analysis indicated that CYP24A1-rs2296241 polymorphism reduced the androgen-related prostate cancer risk in additive and recessive models. More genetic loci are needed to confirm the effect of CYP24A1 variation on the risk of prostate cancer.

SUBMITTER: Wang P

PROVIDER: S-EPMC4447172 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis.

Wang Ping P Zhang Hemei H Zhang Zengli Z Qin Liqiang L Li Bingyan B

OncoTargets and therapy 20150522

<h4>Background</h4>The evidence for vitamin D reducing cancer risk is inconsistent, and it is not clear whether this reduction is related to variation in cytochrome P450 (CYP)24A1, the only enzyme known to degrade active vitamin D. We focused on evaluating the association of CYP24A1-rs2296241 polymorphism with hormone-related cancer risk by conducting a meta-analysis.<h4>Methods</h4>A systematic literature search was conducted in April 2014 (updated in December 2014) to identify eligible studies ...[more]

PMID: 26045671

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Project description:The association between FokI polymorphism in the vitamin D receptor (VDR) gene and susceptibility to arterial hypertension (HT) is controversial. Thus, we evaluated the relation between FokI and HT according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE® (Medical Literature Analysis and Retrieval System Online)/PubMed, Scopus, and Cochrane Library CENTRAL databases. Data from case-control studies, including the number of participants, age, 25-hydroxyvitamin D concentrations, systolic and diastolic blood pressure values, FokI allele, and genotype frequency were extracted by 2 independent authors and OR was calculated with the 95% CI to assess the strength of the association between the FokI variant and odds of HT. In general and subgroup analyses, we used allelic (f compared with F), common (ff compared with FF + Ff), risk (ff + Ff compared with FF), and additive (ff compared with FF) models. Six case-control studies including 3140 cases and 3882 controls were reviewed in the meta-analysis. Global assessment revealed a correlation between FokI and reduced odds of HT in the additive/homozygote model (ff compared with FF; OR: 0.65; 95% CI: 0.45-0.94) and common/recessive model (ff compared with FF + Ff; OR: 0.75; 95% CI: 0.57-0.99). In Asian subjects, there was a significant reduction in the odds of HT in additive (ff compared with FF; OR: 0.84; 95% CI: 0.73-0.98) and risk models (ff + Ff compared with FF; OR: 0.87, 95% CI: 0.78-0.97), in particular, for Indians (South). In Africans, the statistically significant association occurred in the additive and common models. Allele f in the FokI polymorphism of the VDR gene was associated with reduced odds of HT in the general population based on the risk model. Thus, nutritional genomics can help understand the influence of nutrition on metabolic homeostasis pathways and the clinical consequences of hypertension. This study shows the need for healthy, anti-inflammatory, and antioxidant compounds to prevent or treat chronic complications.

Project description:BackgroundCommon polymorphisms of the vitamin D receptor gene have been reported to affect the risk of breast, colon, prostate, and differentiated thyroid cancer (DTC), but polymorphisms within the genes of vitamin D metabolizing enzymes have not been studied in DTC. The aim of the present study was to investigate the genes for vitamin D enzymes in patients with DTC and healthy controls (HC) as well as the vitamin D (25-hydroxyvitamin D(3), and 1,25-hydroxyvitamin) status.MethodsGerman patients (n=253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n=302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25-hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]). Furthermore, the 25-hydroxyvitamin D(3) [25(OH)D(3)] and 1,25-hydroxyvitamin [1,25(OH)(2)D(3)] plasma levels were measured by a radioimmunoassay.ResultsThere was no difference in the genotypes; however, the CYP24A1 haplotype analysis showed that rs2248137C/rs2296241A (13.1% vs. 19.1%; corrected p [pc]=0.04) was less frequent in the PTC, whereas the haplotypes rs2248137C/rs2296241G (56.0% vs. 41.9%; pc=0.03), rs927650C/rs2296241G (22.5% vs. 8.4%; pc=1.6×10(-3)), and rs927650C/rs2248137C/rs2296241G (21.1% vs. 7.3%; pc=1.5×10(-3)) were more frequent in the FTC compared with HC. Furthermore, if patients and controls were grouped according to four 25(OH)D(3) categories (severely deficient, deficient, insufficient, and sufficient), then the patients with both DTC subtypes had significantly lower levels of circulating 1,25(OH)(2)D(3), especially in the group with a deficient 25(OH)D(3) status compared with the controls. Although the polymorphisms showed no differences stratified for the four 25(OH)D(3) categories, the activation status by 1,25(OH)(2)D(3) differed significantly depending on the genotypes of the investigated CYP24A1 polymorphisms.ConclusionsA higher risk for DTC is conferred by haplotypes within the CYP24A1 gene, low circulating 25(OH)D(3) levels (deficiency), and a reduced conversion to 1,25(OH)(2)D(3). These results confirm and extend previous observations and also support a role of the vitamin D system in the pathogenesis of DTC. How deficient 25(OH)D(3) levels in combination with certain CYP24A1 haplotypes affect vitamin D activation is the subject of future studies.

Dataset Information

Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis.

Publications

Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis.

Similar Datasets

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