Meta-analysis of longitudinal studies: Serum vitamin D and prostate cancer risk

Aim: To review and summarize evidence from longitudinal studies on the association between serum 25-hydroxyvitamin D (25(OH)D) and the risk of prostate cancer (PC). Methods: Relevant prospective cohort studies and nested case-control studies published until July 2009 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, PC incidence/PC mortality according to serum vitamin D status and the respective risk ratios, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase in serum 25(OH)D by 10 ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. Results: Overall, eleven original articles were included, ten of which reported on the association between serum vitamin D levels and PC incidence and one article reported on the association with PC mortality. Meta-analysis of studies on PC incidence resulted in a summary OR (95% confidence interval, CI) of 1.03 (0.96–1.11) associated with an increase of 25(OH)D by 10 ng/ml (P = 0.362). No indication for heterogeneity and publication bias was found. Conclusions: According to available evidence from longitudinal studies, serum 25(OH)D is not associated with PC incidence.     

Prediagnostic plasma vitamin D metabolites and mortality among patients with prostate cancer

Background

Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.

Methodology/Principal Findings

We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)₂vitamin D [1,25(OH)₂D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians'' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)₂D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P_trend = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)₂D levels were not associated with lethal prostate cancer.

Conclusions/Significance

Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis.     

Vitamin D,Parathyroid Hormone,and Heart Failure in A Chinese Elderly Population

ObjectiveHeart failure (HF) is a major cause of morbidity and mortality worldwide. Low vitamin D status has been shown to be associated with increased risk of developing cardiovascular disease. In this study, we examined the association between vitamin D and parathyroid hormone (PTH) levels and HF in and elderly population in China.MethodsA population-based cross-sectional study was conducted in the spring of 2013 among 2,047 community-dwelling healthy individuals, aged 60 to 101 years. 25-Hydroxyvitamin D (25[OH]D) was measured using a chemiluminescence assay. PTH levels were measured with an electrochemiluminescence immunoassay.ResultsA total of 2,047 participants, including 1,121 women (54.7%), were evaluated in 2013. The median concentrations of serum 25(OH)D and PTH for the entire group were 16.1 ng/mL and 41.5 pg/mL, respectively. Serum 25(OH)D and PTH levels were associated with serum N-terminal pro-brain natriuretic peptide levels and left ventricular ejection fraction in a multivariate adjusted linear regression analysis (P < .05). In logistic regression analyses, serum 25(OH)D and PTH levels were associated with a risk of HF in single and multiple regression models (P < .05). Compared with patients with 25(OH)D levels between 30.0 and 44.9 ng/mL, patients with 25(OH)D levels less than 10 ng/mL had a higher mean hazard ratio for HF (2.88; 95% confidence interval, 1.59 to 4.38).ConclusionSerum 25(OH)D and PTH levels are independently associated with risk of HF in a Chinese elderly population. (Endocr Pract. 2014;21:30-40)     

Genetic Variants in Vitamin D Pathway Genes and Risk of Pancreas Cancer; Results from a Population-Based Case-Control Study in Ontario,Canada

Recent studies of 25-hydroxyvitamin D (25(OH)D) levels and pancreas cancer have suggested a potential role of the vitamin D pathway in the etiology of this fatal disease. Variants in vitamin-D related genes are known to affect 25(OH)D levels and function and it is unknown if these variants may influence pancreatic cancer risk. The association between 87 single nucleotide polymorphisms (SNPs) in 11 genes was evaluated within the Ontario Pancreas Cancer Study, a population-based case-control study. Pancreatic cancer cases with pathology confirmed adenocarcinoma were identified from the Ontario Cancer Registry (n = 628) and controls were identified through random digit dialing (n = 1193). Age and sex adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. SNPs in the CYP24A1, CYP2R1, calcium sensing receptor (CASR), vitamin D binding protein (GC), retinoid X receptor-alpha (RXRA) and megalin (LRP2) genes were significantly associated with pancreas cancer risk. For example, pancreas cancer risk was inversely associated with CYP2R1 rs10741657 (AA versus GG, OR = 0.70; 95%CI: 0.51–0.95) and positively with CYP24A1 rs6127119 (TT versus CC. OR = 1.94; 95%CI: 1.28–2.94). None of the associations were statistically significant after adjustment for multiple comparisons. Vitamin D pathway gene variants may be associated with pancreas cancer risk and future studies are needed to understand the possible role of vitamin D in tumorigenesis and may have implications for cancer-prevention strategies.     

Hashimoto Thyroiditis not Associated with Vitamin D Deficiency

Objective: Vitamin D deficiency is associated with several autoimmune diseases. This study assessed whether vitamin D deficiency is associated with Hashimoto thyroiditis (HT).Methods: Two groups of patients were selected for which serum 25-hydroxyvitamin D (25(OH)D) levels had been measured: (1) a study group of patients diagnosed with HT as indicated by thyroid antibodies, and (2) a healthy control group. Each group was separated by sex and then controlled for age and body mass index (BMI). Groups' mean 25(OH)D levels were compared by analysis of variance (ANOVA), and percent frequencies of vitamin D sufficiency, insufficiency, and deficiency were compared with a Z-test. The correlations between 25(OH)D levels and thyroid antibodies and thyroid-stimulating hormone (TSH) levels were also tested.Results: The mean 25(OH)D levels for the HT and control groups were significantly different in females (30.75 vs. 27.56 ng/mL, respectively) but not in males (14.24 vs. 13.26 ng/mL). HT females had a higher rate of vitamin D sufficiency (51.7% vs. 31.1%) and a lower rate of insufficiency (48.3% vs. 68.9%) relative to control females. No such differences were found in the male groups. None of the females were vitamin D deficient, but almost all males were. A significant (P = .016) positive correlation (r_s = 0.436) between 25(OH)D and TPOAb was observed in males.Conclusion: HT is not associated with higher rates of vitamin D deficiency relative to a control group.Abbreviations:BMI = body mass indexHT = Hashimoto thyroiditis25(OH)D = 25-hydroxyvitamin DTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTPOAb = thyroid-peroxidase antibodyVDR = Vitamin D receptor     

Prostate Tissue Metal Levels and Prostate Cancer Recurrence in Smokers

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N?=?25) had significantly higher Cd (median ppb, p?=?0.03) and lower Zn (p?=?0.002) in non-neoplastic tissue than never-smokers (N?=?21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p?=?0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p?=?0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p?=?0.039 and adjacent non-neoplastic, p?=?0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.     

Vitamin D,Parathyroid Hormone,and Serum Lipid Profiles in a Middle-Aged and Elderly Chinese Population

ObjectivesTo explore the associations of serum vitamin D and parathyroid hormone (PTH) levels with serum lipid profiles and the risk of hyperlipidemia in a middle-aged and elderly population.MethodsA population-based cross-sectional study was conducted in the spring of 2012 among 1,203 Chinese participants, aged 52 to 101 years. 25-Hydroxyvitamin D [25(OH)D] was measured by chemiluminescence assay. (PTH) levels were measured with an electrochemilumines-cence immunoassay (ECLIA) method.ResultsA total of 1,203 participants, including 526 women (43.7%), were evaluated in 2012. The median concentrations of serum 25(OH)D and PTH for the entire group were 17.3 ng/mL and 38.3 pg/mL, respectively. Serum 25(OH)D and PTH levels were not independently associated with serum total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels in a multivariate adjusted linear regression analysis of 1,027 participants not receiving antihyperlipidemic treatment (P > .05). In logistic regression analyses, serum 25(OH)D and PTH lev-els were not associated with a risk of hyperlipidemia after adjustment for age, sex, heavy drinking, smoking, diabetes, obesity, family history of hyperlipidemia, body mass index (BMI), physical activity, glomerular filtration rate (GFR), fasting glucose, high-sensitivity Creactive protein (hsCRP), calcium, and hemoglobin.ConclusionsSerum 25(OH)D and PTH levels are not independently associated with serum lipid levels or an increased risk of hyperlipidemia in a middle-aged and elderly Chinese population. (Endocr Pract. 2014;20: 556-565)     

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

BackgroundVitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC.MethodsWe recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.Results7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050).ConclusionsWe found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.     

Genetic variations in VDR associated with prostate cancer risk and progression in a Korean population

Low levels of vitamin D are implicated as a potential risk factor for prostate cancer, and the vitamin D receptor (VDR) gene may be important in the onset and progression of prostate cancer. In this study, sequence variants in the VDR gene were investigated in a Korean study cohort to determine whether they are associated with prostate cancer risk. We evaluated the association between 47 single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer risk as well as clinical characteristics (prostate-specific antigen level, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer patients and 173 benign prostatic hyperplasia patient who underwent a prostate biopsy, which was negative for malignancy) using unconditional logistic regression. The statistical analysis suggested that two VDR sequence variants (rs2408876 and rs2239182) had a significant association with prostate cancer risk (odds ratio [OR]. 1.41; p = 0.03; OR, 0.73; p = 0.05, respectively). Logistic analyses of the VDR polymorphisms with several prostate cancer related factors showed that several SNPs were significant; nine SNPs to PSA level, three to clinical stage, two to pathological stage, and three SNPs to the Gleason score. The results suggest that some VDR gene polymorphisms in Korean men might not only be associated with prostate cancer risk but also significantly related to prostate cancer-related risk factors such as PSA level, tumor stage, and Gleason score. However, current limitation for small cohort with not-healthy control group might have false positive effects; therefore it should be overcome via further large-scale validating studies.     

Levels of 25-hydroxyvitamin D in familial longevity: the Leiden Longevity Study

Background:

Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners.

Methods:

We assessed anthropometric characteristics, 25(OH) vitamin D levels, parathyroid hormone levels, dietary vitamin D intake and single nucleotide polymorphisms (SNPs) associated with vitamin D levels. We included offspring (n = 1038) of nonagenarians who had at least one nonagenarian sibling, and the offsprings’ partners (n = 461; controls) from the Leiden Longevity Study. We included age, sex, body mass index, month during which blood sampling was performed, dietary and supplemental vitamin D intake, and creatinine levels as possible confounding factors.

Results:

The offspring had significantly lower levels of vitamin D (64.3 nmol/L) compared with controls (68.4 nmol/L; p = 0.002), independent of possible confounding factors. There was no difference in the levels of parathyroid hormone between groups. Compared with controls, the offspring had a lower frequency of a genetic variant in the CYP2R1 gene (rs2060793) (p = 0.04). The difference in vitamin D levels between offspring and controls persisted over the 2 most prevalent genotypes of this SNP.

Interpretation:

Compared with controls, the offspring of nonagenarians who had at least one nonagenarian sibling had a reduced frequency of a common variant in the CYP2R1 gene, which predisposes people to high vitamin D levels; they also had lower levels of vitamin D that persisted over the 2 most prevalent genotypes. These results cast doubt on the causal nature of previously reported associations between low levels of vitamin D and age-related diseases and mortality.Vitamin D plays a critical role in bone formation,¹ immune cell differentiation, and in the inhibition of proliferation and angiogenesis in cancer.² Low serum levels of 25-hydroxyvitamin D3 (25[OH] vitamin D) are associated with increased mortality, cardiovascular disease, diabetes mellitus, cancer, multiple sclerosis, allergy, asthma, infection, depression, mental illness and musculoskeletal pain.^3–6 However, because of design limitations, previous studies have not been able to infer causality.⁷ A meta-analysis that included 51 studies and more than 30 000 individuals in each treatment group showed no reduction in all-cause or cardiovascular mortality with vitamin D supplementation,⁸ suggesting that low serum levels of vitamin D are a consequence rather than a cause of disease.Vitamin D status is routinely assessed by measurement of serum concentration of the prohormone 25(OH) vitamin D, which is the most stable and abundant metabolite of vitamin D in circulation. In the current study, we investigated the association between serum levels of 25(OH) vitamin D and familial longevity. We assessed vitamin D levels in the offspring of nonagenarian siblings whom we have previously shown to have a lower prevalence of cardiovascular diseases and lower mortality compared to age- and environmental-matched controls.^9,10 We also assessed whether genetic variation in 3 genes¹¹ was associated with 25(OH) vitamin D levels among the offspring of nonagenarians who had at least 1 nonagenarian sibling, and their partners.     

The Association between Pre-Treatment Serum 25-Hydroxyvitamin D and Survival in Newly Diagnosed Stage IV Prostate Cancer

Background/Aims

Emerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients.

Methods

A consecutive cohort of 125 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2011. We used the vitamin D categories of “deficient (<20 ng/ml)”, “insufficient (20 to 32 ng/ml)”, and “sufficient (>32 ng/ml)”. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.

Results

Mean age at diagnosis was 60 years. Of the 125 patients, 32 (25.6%) were deficient, 49 (39.2%) were insufficient and 44 (35.2%) were sufficient in vitamin D at the time of diagnosis. The median survival in deficient, insufficient and sufficient cohorts was 47.8, 44.0 and 52.6 months respectively (p = 0.60). On univariate analysis, four variables demonstrated a statistically significant association with survival: nutritional status, bone metastasis, corrected serum calcium and serum albumin (p<0.05 for all). On multivariate analysis, five variables demonstrated statistically significant associations with survival: hospital location, age, bone metastasis, serum albumin and corrected serum calcium (p<0.05 for all). Serum vitamin D status was not significant on either univariate or multivariate analysis.

Conclusion

Contrary to previously published research, we found no significant association between pre-treatment serum 25(OH)D and survival in newly diagnosed stage IV prostate cancer patients. The lack of a significant association between serum vitamin D and survival in our study could perhaps be due to the fact that the disease was far too advanced in our patients for vitamin D levels to have any impact on prognosis.     

Vitamin D Binding Protein Gene Polymorphism as a Risk Factor for Vitamin D Deficiency in Thais

ObjectiveVitamin D deficiency is related to increased risks for a number of diseases. To date, at least 3 candidate genes, vitamin D binding protein (VDBP) gene (GC), 25-hydroxylase (CYP2R1), and 7-dehydrocholes-terol reductase/NAD synthetase 1 (DHCR7/NADSYN1), have been associated with serum 25-hydroxyvitamin D (25[OH]D) levels, but their influences on the prevalence of vitamin D deficiency in relation to other known risk factors have not been clearly defined.MethodsThe study assessed 4,476 individuals aged 14 to 93 years from the Thailand 4^th National Health Examination Survey (2008-2009) and the Electricity Generating Authority of Thailand (EGAT) (2008) cohorts. The GC rs2282679 polymorphism on chromosome 4q12-q13 was genotyped by real-time polymerase chain reaction (PCR). Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Vitamin D deficiency was defined as a 25(OH)D concentration < 20 ng/mL.ResultsData were expressed as mean ± SD. There were 2,747 (61.4%) males and 1,729 (38.6%) females in the study, with an average body mass index (BMI) of 23.7 ± 4.2 kg/m² and a mean total 25(OH)D of 28.9 ± 9.0 ng/mL. Serum 25(OH)D levels decreased progressively with the presence of the C allele. Using multiple logistic regression analysis, vitamin D deficiency was significantly associated with the GC rs2282679 genotype (odds ratio [OR] per C allele 1.80, 95% confidence interval CI 1.57-2.01), independent of established risk factors for vitamin D deficiency including age, sex, and BMI.ConclusionA specific GC gene polymorphism is associated with lower 25(OH)D levels independent of age, sex, and adiposity in Thai subjects. (Endocr Pract. 2015;21:221-225)     

The Importance of Vitamin D Level in Subacute Thyroiditis Disease and the Effect of Vitamin D on Disease Prognosis

Objective: Subacute thyroiditis (SAT) is an inflammatory thyroid disease that manifests with severe pain. The presence of the vitamin D receptor in immune system cells shows that vitamin D deficiency can trigger inflammatory diseases. The aim of the present study was to determine the prevalence of vitamin D deficiency in SAT patients, and the relationship between vitamin D level and permanent hypothyroidism and recurrence rate.Methods: In this retrospective study, 25-hydroxyvitamin D (25&lsqb;OH]D) levels of 170 SAT patients and 86 control subjects were compared.Results: The 25(OH)D levels were significantly lower in the SAT patients, and there was no seasonal difference. A negative correlation was determined between the erythrocyte sedimentation rate and 25(OH)D, but no significant relationship was found between vitamin D level and prognosis.Conclusion: As a result of this study, it was shown that vitamin D levels in subacute thyroiditis patients were significantly lower than in the healthy control group. Although there is no relationship between vitamin D level and disease prognosis, vitamin D deficiency may increase the rate of respiratory tract infections (especially, influenza, coxsackievirus, measles, adenovirus, retroviruses) and eventually SAT development.     

Common variation in vitamin D pathway genes predicts circulating 25-hydroxyvitamin D Levels among African Americans

Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions.     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)     

Vitamin d, parathyroid hormone and their associations with hypertension in a chinese population

Background

Conflicting reports support or refute an association between vitamin D deficiency with high levels of parathyroid hormone (PTH) and raised blood pressure or hypertension.

Objective

To explore the associations of serum vitamin D and PTH levels with blood pressure and risk of hypertension in a Chinese population.

Methods

A population-based cross-sectional study was conducted among 1,420 Chinese participants, aged 20–83 years, in 2010. Anthropometric phenotypes and blood pressure were evaluated. Serum lipids, 25-hydroxyvitamin D [25(OH)D] and PTH were measured.

Results

One thousand four hundred and twenty participants, including 566 women (39.9%), were evaluated in 2010. Four hundred and eighty seven were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The median concentrations of serum 25(OH)D and PTH were 22.0 ng/ml and 2.83 pmol/l, respectively. Serum 25(OH)D and natural log of PTH levels were not independently associated with blood pressure in a multivariable adjusted linear regression analysis of 1,206 participants not receiving antihypertensive treatment (P>0.05). In logistic regression analyses, serum 25(OH)D levels were not associated with risk of hypertension in single and multiple regression models. One unit increments of natural log of PTH levels were significantly associated with risk of hypertension in the crude model (OR = 1.78, 95% confidence interval 1.38–2.28, P<0.0001) and model adjusted for age and sex (OR = 1.41, 95% confidence interval 1.08–1.83, P = 0.01). However, these associations were attenuated and became nonsignificant (OR = 1.29, 95% confidence interval 0.98–1.70, P = 0.07) after further adjustment for body mass index, current alcohol intake, current smoking, glomerular filtration rate and family history of hypertension.

Conclusions

Serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population.     

The association between fat mass and obesity-associated (FTO) genotype and serum vitamin D level in breast cancer patients

The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross-sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra-primer amplification refractory mutation system (Tetra-ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme-linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.     

Low Vitamin D Status and Suicide: A Case-Control Study of Active Duty Military Service Members

Objective

Considering that epidemiological studies show that suicide rates in many countries are highest in the spring when vitamin D status is lowest, and that low vitamin D status can affect brain function, we sought to evaluate if a low level of 25-hydroxyvitamin D [25(OH)D] could be a predisposing factor for suicide.

Method

We conducted a prospective, nested, case-control study using serum samples stored in the Department of Defense Serum Repository. Participants were previously deployed active duty US military personnel (2002–2008) who had a recent archived serum sample available for analysis. Vitamin D status was estimated by measuring 25(OH) D levels in serum samples drawn within 24 months of the suicide. Each verified suicide case (n = 495) was matched to a control (n = 495) by rank, age and sex. We calculated odds ratio of suicide associated with categorical levels (octiles) of 25(OH) D, adjusted by season of serum collection.

Findings

More than 30% of all subjects had 25(OH)D values below 20 ng/mL. Although mean serum 25(OH)D concentrations did not differ between suicide cases and controls, risk estimates indicated that subjects in the lowest octile of season-adjusted 25(OH)D (<15.5 ng/mL) had the highest risk of suicide, with subjects in the subsequent higher octiles showing approximately the same level of decreased risk (combined odds ratio compared to lowest octile  = 0.49; 95% C.I.: 0.315–0.768).

Conclusions

Low vitamin D status is common in active duty service members. The lowest 25(OH)D levels are associated with an increased risk for suicide. Future studies could determine if additional sunlight exposure and vitamin D supplementation might reduce suicide by increasing 25(OH) D levels.     

Long Term Association between Serum 25-Hydroxyvitamin D and Mortality in a Cohort of 4379 Men

Objective

A number of observational studies have shown an inverse association between circulating 25-hydroxyvitamin D and total mortality, but a reverse J-shaped association has also been reported. In a large nested case-control study, serum-25-hydroxyvitamin D (s-25(OH)D) was positively associated with incident prostate cancer. Based on the same study population, the primary aim of the present study was to investigate the association between s-25(OH)D and total mortality.

Methods

Men participating in population based health screenings during 1981–1991 and enrolled in a nested case-control study were followed throughout 2007 with respect to all-cause and cause-specific mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression.

Results

In men with prostate cancer (n = 2282), there was a significant inverse association between s-25(OH)D and total mortality after controlling for potential confounders (HR = 1.25 (95% CI 1.05–1.50), s-25(OH)D <50 nmol/l versus s-25(OH)D ≥50 nmol/l). The corresponding figure among controls (n = 2147) was HR = 1.15 (95% CI 0.88–1.50) and in the total study population HR = 1.19 (95% CI 1.03–1.38). For cause-specific deaths, we found no significant associations.

Conclusions

In this study population, s-25(OH)D was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high s-25(OH)D was associated with increased risk of prostate cancer.     

Low Serum 25-Hydroxyvitamin D Concentrations Are Associated with Increased Risk for Melanoma and Unfavourable Prognosis

Background

Low vitamin D status (serum 25(OH)D concentration) is associated with increased incidence and unfavourable outcome of various types of cancer. However, there are limited data on influence of serum 25(OH)D on risk and prognosis of malignant melanoma.

Methods

Basal serum 25(OH)D concentrations were retrospectively analyzed in a cohort of melanoma patients (n = 324) and healthy controls (n = 141). We tested the hypothesis that serum 25(OH)D concentrations are predictive of melanoma risk, thickness of primary melanomas, and overall survival (OS).

Results

Median serum 25(OH)D concentrations were significantly lower (p = 0.004) in melanoma patients (median = 13.6 ng/ml) as compared to controls (median = 15.6 ng/ml). Primary tumors of patients with low serum 25(OH)D concentrations (<10 ng/ml) had significantly (p = 0.006) greater Breslow thickness (median: 1.9 mm) as compared to patients with higher levels (>20 ng/ml; median: 1.00 mm). Patients with 25(OH)D serum concentrations in the lowest quartile had inferior overall survival (median: 80 months) comparing with the highest quartile (median: 195 months; p = 0.049).

Conclusions

Our data support the concept that serum 25(OH)D concentrations are associated with risk and prognosis of melanoma. Whether normalizing serum 25(OH)D concentrations in these patients improves outcomes will require testing in future clinical trials.