Circulating 25-Hydroxy Vitamin D Relative to Vitamin D Receptor Polymorphism after Vitamin D3 Supplementation in Breast Cancer Women: A Randomized,Double-Blind Controlled Clinical Trial

Objective: The influence of vitamin D receptor (VDR) genetic variation on serum 25-hydroxyvitamin D levels [25(OH)D] after vitamin D3 supplementation remains unclear. We aimed to investigate changes of 25(OH)D in a randomized, double-blind, placebo-controlled clinical trial, according to VDR genotype, after provision of vitamin D3 to breast cancer cases for a 2-month period. Methods: Participants were assigned to two treatment arms: placebo (n = 28) and vitamin D3 supplementation (n =28). The supplementation group received 50,000 IU of vitamin D every week for 2 months. Blood samples were collected at baseline and after intervention to measure serum 25(OH) D3. Genotypes were assessed for FokI, BsmI, ApaI, and TaqI polymorphisms. Results: After eight weeks supplementation, the rvention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004). Subjects were then classified into twelve subgroups according to different VDR genotypes. Subjects with ff/Ff, TT/Tt, and Bb genotypes had significantly higher increases in serum 25(OH)D compared to those with FF, tt, and BB/bb genotypes post-intervention. Serum vitamin D3 levels with the AA genotype were lower than with aa/ Aa. No differences were found among other subgroups. Conclusion: Vitamin D3 supplementation increases serum 25(OH)D in women with breast cancer. Serum vitamin D3 in TT/Tt, ff/Ff, and Bb carriers was more responsive to vitamin D supplementation than in those with FF/ff and tt genotypes. Other subgroups might gain less from vitamin D3 supplementation.     

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitaminD3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstratethe power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDRpolymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation onthe serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in theVDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention.Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and afterthe intervention to measure the 25(OH) D3, TNF-α, TGF- β and TAC. Genotyping was performed for FokI, BsmI, ApaI,and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increasein the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017).Changes in TNF-α, TGF- β1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes weremore responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breastcancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive tovitamin D supplement compared with those with the FF/ff and tt genotypes.     

The Fok1 Vitamin D Receptor Gene Polymorphism and 25(OH) D Serum Levels and Prostate Cancer among Jordanian Men

Background: Prostate cancer (PCa) is one of the most commonly diagnosed neoplasms and the second leadingcause of cancer death in men in the Western world. Vitamin D (1,25dihydroxy vitamin D) is linked to manybiological processes that influence oncogenesis but data on relations between its genetic variants and cancerrisk have been inconsistent. The aim of this study was to determine associations between a vitamin D geneticpolymorphism and 25-hydroxyvitamin D [25(OH)D] levels and prostate cancer. Materials and Methods: GenomicDNA was extracted from 124 Jordanian prostate cancer patients and 100 healthy volunteers. Ethical approvalwas granted from the ethical committee at Hashemite University and written consent was given by all patients.PCR was used to amplify the vitamin D receptor Fok1 polymorphism fragment. 25(OH)D serum levels weremeasured by competitive immunoassay. Results: All genotypes were in Hardy-Weinberg equilibrium. Genotypefrequency for Fok1 genotypes FF, Ff and ff was 30.7%, 61.3% and 8.06%, for prostate cancer patients, whilefrequencies for the control group was 28.0%, 66.0% and 6.0%, respectively, with no significant differences.Vitamin D serum level was significantly lower in prostate cancer patients (mean 7.7 ng/ml) compared to the controlgroup (21.8 ng/ml). No significant association was noted between 25(OH)D and VDR Fok1 gene polymorphismamong Jordanians overall, but significant associations were evident among prostate cancer patients (FF, Ff andff : 25(OH)D levels of 6.2, 8.2 and 9.9) and controls (19.0, 22.5 and 26.3, respectively). An inverse associationwas noted between 25(OH)D serum level less than 10ng/ml and prostate cancer risk (OR 35.5 and 95% CI 14.3-88.0). Conclusions: There is strong inverse association between 25(OH)D serum level less than 10ng/ml leveland prostate cancer risk.     

Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas.

Experimental studies suggest that vitamin D and calcium protect against cancer by reducing proliferation and inducing differentiation. The effects of vitamin D and calcium may be mediated by the vitamin D receptor (VDR), which is encoded by the VDR gene. The present study investigated whether calcium intake and serum vitamin D, as an integrated measure of intake and endogenous production, were associated with risk of colorectal adenoma, known precursors of invasive colorectal cancer. In addition, the interrelation among vitamin D, calcium, and FokI polymorphism of the VDR gene was investigated. Persons (239) with histologically confirmed colorectal adenomas and 228 control individuals without colorectal adenomas confirmed by sigmoidoscopy were enrolled in this case control study conducted at the National Naval Medical Center, Bethesda, MD. We observed an inverse association of serum 25-OH vitamin D [25-(OH)D] with colorectal adenoma. With each 10 ng/ml increase of serum 25-(OH)D, the risk of colorectal adenoma decreased by 26% (odds ratio 0.74, 95% confidence interval 0.60-0.92). The results provided limited evidence for a weak association between calcium intake and colorectal adenoma (odds ratio 0.97, 95% confidence interval 0.93-1.01 per each 100-mg calcium intake). However, the inverse association of serum 25-(OH)D with colorectal adenoma is suggested to be stronger in subjects with calcium intake above the median (P for multiplicative interaction 0.13). The VDR FokI polymorphism was not significantly associated with colorectal adenoma and did not modify the effect of vitamin D or calcium. In conclusion, the study results suggested a protective effect for vitamin D on colorectal adenoma.     

Serum vitamin D concentration,vitamin D-related polymorphisms,and colorectal cancer risk

Serum 25-hydroxyvitamin D (25(OH)D) has been demonstrated to be associated with risk of colorectal cancer (CRC). However, it remains unclear whether this association was modified by vitamin D-related polymorphisms. We evaluated association of serum 25(OH)D concentration with CRC risk among 403 170 participants from UK Biobank Project. Two variants of vitamin D binding protein (VDBP), rs4588 and rs7041, were included to estimate the binding affinity of 25(OH)D to VDBP, and three variants of vitamin D receptor (VDR), rs11568820, rs2228570 and rs1544410, which may influence VDR activity, were also investigated. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 4 957 677 person-years of follow-up, 5053 incident CRC cases were documented. Higher serum 25(OH)D concentrations were significantly associated with lower CRC incidence in a dose-response manner, with HR (95% CIs) being 0.94 (0.91-0.97) per 1 SD increment of serum 25(OH)D level (P_trend < .001). When separated by anatomic site, we observed a significant association between higher 25(OH)D and lower incidence of colon cancer (P_trend < .001), but not rectal cancer (P_trend = .880). The inverse associations between 25(OH)D level and CRC risk were demonstrated in almost all individuals carrying different GC or VDR genotypes, except for those with rs1544410 TT or rs4588 TT genotypes. There was no significant interaction between any single variant, or haplotypes of GC or VDR, and 25(OH)D level. Our findings suggest the potential benefits of maintaining adequate vitamin D for CRC prevention, particularly for tumors from colon.     

Associations between Vitamin D Receptor (VDR) Gene Polymorphisms and Colorectal Cancer Risk and Effect Modifications of Dietary Calcium and Vitamin D in a JapanesePopulation

Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphismsand colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a studyof 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI,BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calciumand vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to beassociated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio ofcolorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidenceinterval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreasedrisk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with highcalcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk ofcolon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphismswere unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin Dintake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer inJapanese, dependent on dietary calcium intake.     

Vitamin D and breast cancer: Emerging concepts

The benefit of vitamin D in cancer prevention and to certain extent therapy has been well recognized. The active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2 D3) is a natural ligand for vitamin D receptor (VDR). Since 1,25(OH)2D3 exerts toxic effects at a concentration that is beneficial, nearly 1500 analogs of vitamin D have been synthesized and evaluated for their efficacy in a variety of carcinogenesis and human cancer models both in vitro and in vivo. Among these only a handful of them have been approved for evaluation in clinical trials for leukemia, breast, prostate and colon cancers. The mechanism of vitamin D action is mediated by the nuclear VDR and the signaling cascade for its action is extensively reported. In this review we focus on the newer concepts for vitamin D action. These include (1) differential effects of vitamin D in maintaining cell proliferation when the cells are under stress but suppressing cell growth when the cells are transformed; (2) functional significance of VDR polymorphism in potential vitamin D responsiveness; (3) regulation of constitutive splicing of vitamin D target gene, CYP24a, by the hormone and its significance; and (4) regulation of microRNA by vitamin D in breast cancer. It is anticipated that the new work in these selective areas would expand the understanding of vitamin D in breast cancer prevention and therapy.     

Genetic Polymorphisms of Vitamin D Receptor Gene are Associated with Cervical Cancer Risk in Northeastern Thailand

Objective: This study aimed to explore whether VDR polymorphisms (Fok1, Apa1 and Taq1) are associated to the cervical cancer in Thai population. Materials and methods: Subjects of 204 cervical cancer patient and 204 age-matched healthy control were enrolled in the case-control study. VDR polymorphisms were detected by using real-time PCR. Haplotype analysis of three loci was applied to the obtained genotypes. Results: Significantly increased risk for cervical cancer was observed in carriers of TT genotype (p = 0.0388) and T allele (p = 0.0357) of Fok1 and TC genotype (p = 0.0001), CC genotype (p = 0.0160) and the C allele of Taq1 (p = 0.0001). Haplotype analyses revealed a significant correlation between C-T-C, T-G-C and T-T-C haplotypes and elevated risk for cervical cancer (OR = 2.06; 95%CI = 1.06-4.00; p = 0.0313, OR = 2.15; 95%CI = 1.22-3.80; p = 0.0078 and OR = 2.81; 95%CI = 1.53-5.16; p = 0.0006, respectively). Furthermore, haplotype carrying C allele of Taq1 (C-G-C + C-T-C + T-G-C + T-T-C) significantly increased cervical cancer risk with OR of 1.92 (95%CI = 1.32-2.79, p = 0.0006). Conclusion: Our finding revealed an association between VDR polymorphisms and cervical cancer risk. Taq1 C allele might be a molecular marker for cervical cancer development.     

Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding

Vitamin D has anticarcinogenic properties and might influence colorectal cancer (CRC) risk, but the epidemiological evidence is inconsistent. Many mechanisms of action for vitamin D have been proposed, with some of them initiating via its binding to the vitamin D receptor (VDR). Using a large Scottish case-control study, we investigated (i) main associations between CRC, vitamin D and calcium dietary intake and 4 VDR single nucleotide polymorphisms (rs10735810, rs1544410, rs11568820, rs7975232) and (ii) interaction associations between the VDR variants, vitamin D and calcium intakes. Inverse and dose-dependent associations were found between CRC risk, dietary [Odds ratio (OR) = 0.77, 95% confidence intervals (CI) 0.63, 0.92, p-trend = 0.012] and total vitamin D (OR = 0.80, 95% CI 0.65, 0.98, p-trend = 0.014) intake in multivariable-adjusted logistic regression models, whereas neither calcium intake nor any of the VDR variants were associated with CRC. Additionally, we observed statistically significant interactions (case-control, case-only designs) between vitamin D and calcium intake and rs10735810 (p-interaction 0.02, 0.006, respectively). We conducted meta-analyses of cohort, case-control and serum studies that also showed an inverse association between dietary vitamin D intake and CRC (serum studies: combined OR = 0.70, 95% CI 0.56, 0.87). The evidence of interaction we report here further supports the inverse association between vitamin D mediated through binding to the VDR.     

Dietary calcium, vitamin D, VDR genotypes and colorectal cancer

The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case-control studies of colon and rectal cancer (n = 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3' untranslated region poly-A length polymorphism (designated S for short and L for long). The SS genotype reduced risk of colorectal cancer for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55-0.92). High levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95% CI = 0.24-0.64) but were not associated with rectal cancer in men (OR = 1.02; 95% CI = 0.66-1.56). Similar reduced rectal cancer risk among women was observed at high levels of vitamin D (OR = 0.52; 95% CI = 0.32-0.85) and low-fat dairy products (OR = 0.61; 95% CI = 0.39-0.94). High levels of sunshine exposure reduced risk of rectal cancer among those diagnosed when <60 years of age (OR = 0.62, 95% CI = 0.42-0.93). Examination of calcium in conjunction with VDR genotype showed that a significant 40% reduction in risk of rectal cancer was observed for the SS or BB VDR genotypes when calcium intake was low (p interaction = 0.01 for calcium interaction). For colon cancer, high levels of dietary intake of calcium, vitamin D, and low-fat dairy products reduced risk of cancer for the SS or BB VDR genotypes, although the p for interaction was not statistically significant. These data support previous observations that high levels of calcium and vitamin D reduce risk of rectal cancer and provide support for a weak protective effect for the SS and BB VDR genotypes. The risk associated with VDR genotype seems to depend upon the level of dietary calcium and vitamin D and tumor site.     

1,25(OH)2D3 Attenuates IL-1b-Induced Epithelial-to-Mesenchymal Transition Through Inhibiting the Expression of lncTCF7

The activated form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates numerous cellular processes, including inhibition of cancer progression. IL-1 has been reported to facilitate cancer development, especially by inducing an epithelial-to-mesenchymal transition (EMT) in several malignant tumors. However, the underlying mechanism of 1,25(OH)2D3 and IL-1 in colorectal cancer (CRC) still remains largely unknown. To fill in this knowledge gap, we measured cell proliferation and invasion by CCK-8 and Transwell assays after stimulation with 1,25(OH)2D3 and IL-1 . E-cadherin and vimentin were chosen as markers of EMT measured by immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot. The expression and function of the vitamin D receptor (VDR) was evaluated by Western blot and luciferase reporter assay. qRT-PCR and RNA-FISH were performed to detect the expression and location of lncTCF7 in vitro. The binding sites of VDR in the lncTCF7 promoter were confirmed by a chromatin immunoprecipitation assay. Based on the above experiments, we found that 1,25(OH)2D3 attenuates IL-1 - induced increased proliferation and invasion in colorectal cancer through enhancing VDR, which inhibits the expression of lncTCF7 by directly binding to its promoter region.     

Sun Exposure Makes no Discrimination based on Vitamin D Status and VDR-Foki Polymorphisms for Non-Melanoma Skin Cancers Risk in Iranian Subjects: A Case-Control Study

Background and Objective: Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancers (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with various malignancies. This study aimed to examine the associations between vitamin D status and VDR FokI polymorphisms in Iranian subjects with NMSC. Materials and Methods: This case-control study included 73 diagnosed cases of NMSC and 72 healthy controls from dermatology clinics at Razi Hospital, Tehran, Iran. A questionnaire was used to assess sunlight exposure. The extracted DNA from whole blood samples was genotyped and serum concentrations of 25-hydroxycalciferol (25(OH)D)) and intact parathyroid hormone (iPTH) were measured. Results: We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D and iPTH concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78 and 46.0±20 vs. 40.5±23 pg/mL, p=0.14, respectively). We did not observe any significant increased risk of NMSC due to f allele, as compared with FF (OR =2.33, 95% CI 0.81-6.75, p=0.12). Conclusion: Though sunlight exposure was associated with increased NMSC risk, there were no significant associations between vitamin D status or VDR FokI polymorphisms with NMSC development in our subjects.     

Vitamin D Receptor BsmI Polymorphism and Colorectal Cancer Risk: an Updated Analysis

Background: Previous studies have investigated the association between the vitamin D receptor (VDR) BsmI polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. Materials and Methods: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before November 2013. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) for VDR BsmI polymorphism and CRC were calculated in a fixedeffects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results: This meta-analysis included 14 case-control studies, which included 10,822 CRC cases and 11,779 controls. Overall, the variant genotype (BB) of the BsmI was associated with a lower CRC risk when compared with the wild-type bb homozygote (OR=0.66, 95%CI: 0.49-0.88). Similarly, a decreased CRC risk was also found in the dominant and recessive models. When stratifying for ethnicity, source of controls, and study sample size, associations were observed among Caucasians, population-based studies and studies with large study sample size (>1000 subjects). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. Conclusions: This updated meta-analysis suggests that the VDR BsmI polymorphism may be associated with a moderate protective effect against CRC.     

Associations of Probiotics with Vitamin D and Leptin Receptors and their Effects on Colon Cancer

Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studieshave suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancerdevelopment. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with coloncancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associatedwith other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptinand patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, thecollected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lacticacid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have beencorrelated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recentprogress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.     

Vitamin D Receptor in Breast Cancer Tissues and Its Relation to Estrogen Receptor Alpha (ER-α) Gene Expression and Serum 25-hydroxyvitamin D Levels in Egyptian Breast Cancer Patients: A Case-control Study

IntroductionThis study aimed to explore the role of vitamin D receptor (VDR) in breast cancer tissues and its relation to serum 25-hydroxyvitamin D [25(OH)D] levels and estrogen receptor alpha (ER-α) gene expression in patients with breast cancer.Patients and MethodsCancerous and normal breast tissues from 40 women with breast cancer were analyzed for quantification of VDR levels and ER-α gene expression. The serum levels of 25(OH)D were measured in patients with breast cancer and controls by radioimmunoassay.ResultsPatients with breast cancer had serum levels of 25(OH)D significantly lower than normal control subjects. The levels of VDR and ER-α were significantly higher in breast cancer tissues than in normal breast tissues. The serum levels of 25(OH)D were indirectly and significantly correlated with the tissue levels of both VDR and ER-α gene expression. There was a significant direct correlation between the tissue levels of VDR and ER-α gene expression. The serum 25(OH) D levels, tissue VDR levels, and ER-α gene expression levels were inversely and significantly correlated with breast cancer histopathologic grade. Women with serum 25(OH)D levels ≤ 30 nmol/L, tissue levels of VDR > 5 ng/mL, and tissue levels of ER-α gene expression > 17.7 copies had significantly increased risk for breast cancer incidence.ConclusionWomen with low serum 25(OH)D levels, high tissue levels of VDR, and ER-α gene expression had increased risk for breast cancer. VDR are upregulated in breast cancer tissues thus it may be used for target therapy especially in hormone-negative breast cancer.     

Association of Vitamin D Level with Clinicopathological Features in Breast Cancer

A population-based relationship between low vitamin D status and increased cancer risk is now generallyaccepted. However there were only few studies reported on prognostic impact. To determine the effect of lowvitamin D on progression of breast cancer, we conducted a cross-sectional analysis of vitamin D levels and clinicopathologicalcharacteristics in 200 cases of breast cancer diagnosed during 2011-2012 at the National CancerInstitute of Thailand. Vitamin D levels were measured by high-performance liquid chromatography (HPLC). Clinical and pathological data were accessed to examine prognostic effects of vitamin D. We found that themean vitamin D level was 23.0±6.61 ng/ml. High vitamin D levels (≥32 ng/ml) were detected in 7% of patients,. low levels (<32 ng/ml) in 93% Mean vitamin D levels for stages 1-4 were 26.1±6.35, 22.3±6.34, 22.2±6.46 and21.3±5.42 ng/ml respectively (P=0.016) and 24.1 and 21.3 ng/ml for lymph node negative and positive cases(P=0.006). Low vitamin D level (<32 ng/ml) was significantly found in majority of cases with advanced stage ofthe disease (P=0.036), positive node involvement (P=0.030) and large tumors (P=0.038). Our findings suggestthat low and decreased level of vitamin D might correlate with progression and metastasis of breast cancer.     

Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population.

There is increasing evidence that vitamin D can protect against breast cancer. The actions of vitamin D are mediated via the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered breast cancer risk in a UK Caucasian population. We recruited 241 women following a negative screening mammogram and 181 women with known breast cancer. The VDR polymorphism Bsm I, an intronic 3' gene variant, was significantly associated with increased breast cancer risk: odds ratio bb vs BB genotype = 2.32 (95% CI, 1.23-4.39). The Bsm I polymorphism was in linkage disequilibrium with a candidate translational control site, the variable length poly (A) sequence in the 3' untranslated region. Thus, the 'L' poly (A) variant was also associated with a similar breast cancer risk. A 5' VDR gene variant, Fok I, was not associated with breast cancer risk. Further investigations into the mechanisms of interactions of the VDR with other environmental and/or genetic influences to alter breast cancer risk may lead to a new understanding of the role of vitamin D in the control of cellular and developmental pathways.     

Lack of Associations between Vitamin D Metabolism-Related Gene Variants and Risk of Colorectal Cancer

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluatedgenetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D bindingprotein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1).Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled inthis case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results:In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714),and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRCand the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status,NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants andCRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC,and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledgehas not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless,our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesisneed to be further investigated.     

Vitamin D Deficiency Associated with Differentiated Thyroid Carcinoma: A Case- Control Study

Objective: In recent decades, the incidence of thyroid cancer has increased throughout the world. It is unclear whether factors such as vitamin D deficiency may have been involved in this increase. The present case-control study was conducted to examine any association between Vitamin D deficiency and thyroid cancers. Methods: The study was conducted on 85 patients with differentiated thyroid cancer diagnosed based on fine needle aspiration biopsy as the case group and 85 healthy controls. Serum levels of vitamin D were evaluated before thyroidectomy. For each patient in the case group, one healthy euthyroid person without any thyroid nodules from the general population matched based on season, sex, age (± 1 year) and BMI (± 1) was selected. Finally, 85 pairs were obtained considering inclusion and exclusion criteria. Thyroid function, thyroid antibodies and serum vitamin D were assessed and thyroid sonography was performed in all participants. Results: In the patient group, 72 (85%) were female and 13 (15%) were male. The mean (SD) serum vitamin D level was 8.00 (±3.7) in patient group, as compared to 13.4 (±7.90) in the control group, the difference being significant (OR: 6, 95 % CI: 1.02-113.3; P=0.046). Conclusion: A significant association was noted between vitamin D deficiency and differentiated thyroid cancer. Further studies with a prospective design are necessary to further define the roles of this factor.