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Background: Prior evidence of a possible link between vitamin D status and hematologic malignancy (HM) in humans comes from observational studies, leaving unresolved the question of whether a true causal relationship exists., Methods: The authors performed a secondary analysis of data from the Women's Health Initiative Calcium/Vitamin D (CaD) trial, a large randomized controlled trial of CaD supplementation compared with placebo in older women. Kaplan-Meier and Cox proportional hazards survival analysis methods were used to evaluate the relationship between treatment assignment and 1) incident HM and 2) HM-specific mortality over 10 years following randomization. HMs were classified by cell type (lymphoid, myeloid, or plasma cell) and analyzed as distinct endpoints in secondary analyses., Results: A total of 34,763 Women's Health Initiative CaD trial participants (median age, 63 years) had complete baseline covariate data and were eligible for analysis. Women assigned to CaD supplementation had a significantly lower risk of incident HM (hazard ratio [HR], 0.80; 95% confidence interval [95% CI], 0.65-0.99) but not HM-specific mortality (HR, 0.77 [95% CI, 0.53-1.11] for the entire cohort; and HR, 1.03 [95% CI, 0.70-1.51] among incident HM cases after diagnosis). In secondary analyses, protective associations were found to be most robust for lymphoid malignancies, with HRs of 0.77 (95% CI, 0.59-1.01) and 0.46 (95% CI, 0.24-0.89), respectively, for cancer incidence and mortality in those assigned to CaD supplementation., Conclusions: The current post hoc analysis of data from a large and well-executed randomized controlled trial demonstrates a protective association between modest CaD supplementation and HM risk in older women. Additional research concerning the relationship between vitamin D and HM is warranted. Cancer 2017;123:4168-4177. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose of Review: To briefly review recent work within the vitamin D and cancer field, whereas also providing context relating how these findings may impact clinical care and future research efforts., Recent Findings: Vitamin D has now been convincingly shown both in vitro and in preclinical animal models to alter the differentiation, proliferation, and apoptosis of cancer cells. Whether vitamin D prevents cancer in humans or limits cancer progression, however, remain open questions. Epidemiologic and observational data relating circulating 25(OH)D levels and cancer risk suggest an inverse relationship for most cancers including breast, colorectal, leukemia and lymphoma, and prostate, although for each malignancy there also exist studies that have failed to demonstrate such an inverse relationship. Likewise, a more recent report failed to confirm a previously reported association of increased pancreatic cancer risk in patients with higher 25(OH)D levels. A large prospective study in which patients aged at least 50 years receive 2000 IU vitamin D3 daily for 5 years, with cancer as a primary endpoint, has recently been launched., Summary: Although much effort has attempted to delineate a causal relationship between vitamin D and a wide array of human cancers, we await large-scale randomized controlled trial data for definitive answers.

Objective: The association of hypovitaminosis D with measures of depressive symptoms and cognitive impairment remains unclear. This correlation and subsequent prescribing practices of vitamin D supplementation were evaluated in a population of psychiatric inpatients., Methods: A retrospective study was conducted of 548 patients with a serum 25-hydroxyvitamin D [25(OH)D] level measured during hospitalization. Outcomes included the association of hypovitaminosis D with Patient Health Questionnaire (PHQ-9) and Folstein Mini-Mental State Exam (MMSE) scores, including an evaluation of vitamin D dosing upon hospital discharge., Results: Two hundred three patients (37%) had hypovitaminosis D. The majority [183 (90%)] had moderate (10-24 ng/mL), while 20 (10%) had severe hypovitaminosis D (<10 ng/mL). There was no significant association between hypovitaminosis D and PHQ-9 or MMSE scores (p = 0.107 and p = 0.271, respectively). Overall, 33% of patients with moderate hypovitaminosis D and 45% of patients with severe hypovitaminosis D were newly prescribed vitamin D or received a dose increase. Initiation of vitamin D or increased vitamin D dose was significantly higher in patients with hypovitaminosis D (p < 0.001)., Conclusions: No association was found between hypovitaminosis D and depressive symptoms or cognitive function. However, patients with hypovitaminosis D were more likely to be prescribed additional vitamin D at hospital discharge., (Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: It has been hypothesized that vitamin D mediates the inverse relationship between sun exposure and non-Hodgkin lymphoma (NHL) risk reported in several recent studies. We evaluated the association of self-reported sun exposure at ages <13, 13-21, 22-40, and 41+ years and 19 single nucleotide polymorphisms (SNPs) from 4 candidate genes relevant to vitamin D metabolism (RXR, VDR , CYP24A1, CYP27B1) with NHL risk., Methods: This analysis included 1,009 newly diagnosed NHL cases and 1,233 frequency-matched controls from an ongoing clinic-based study. Odds ratios (OR), 95 % confidence intervals (CI), and tests for trend were estimated using unconditional logistic regression., Results: There was a significant decrease in NHL risk with increased sun exposure at ages 13-21 years (OR(≥15 vs. ≤3 h/week) = 0.68; 95 % CI, 0.43-1.08; p(trend) = 0.0025), which attenuated for older ages at exposure. We observed significant main effect associations for 3 SNPs in VDR and 1 SNP in CYP24A1: rs886441 (OR(per-allele) = 0.82; 95 % CI, 0.70-0.96; p = 0.016), rs3819545 (OR(per-allele) = 1.24; 95 % CI, 1.10-1.40; p = 0.00043), and rs2239186 (OR(per-allele) = 1.22; 95 % CI, 1.05-1.41; p = 0.0095) for VDR and rs2762939 (OR(per-allele) = 0.85; 95 % CI, 0.75-0.98; p = 0.023) for CYP24A1. Moreover, the effect of sun exposure at age 13-21 years on overall NHL risk appears to be modified by germline variation in VDR (rs4516035; p(interaction) = 0.0066). Exploratory analysis indicated potential heterogeneity of these associations by NHL subtype., Conclusion: These results suggest that germline genetic variation in VDR, and therefore the vitamin D pathway, may mediate an association between early life sun exposure and NHL risk.

Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratio[HR] = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.

Purpose: Vitamin D insufficiency is common in the United States, with low levels linked in some studies to higher cancer incidence, including non-Hodgkin's lymphoma (NHL). Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers, although there are no data for NHL., Patients and Methods: We tested the hypothesis that circulating 25-hydroxyvitamin D [25(OH)D] levels are predictive of event-free survival (EFS) and overall survival (OS) in a prospective cohort of 983 newly diagnosed patients with NHL. 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were measured by liquid chromatography-tandem mass spectrometry., Results: Mean age at diagnosis was 62 years (range, 19 to 94 years); 44% of patients had insufficient 25(OH)D levels (< 25 ng/mL) within 120 days of diagnosis. Median follow-up was 34.8 months; 404 events and 193 deaths (168 from lymphoma) occurred. After adjusting for known prognostic factors and treatment, 25(OH)D insufficient patients with diffuse large B-cell lymphoma (DLBCL) had inferior EFS (hazard ratio [HR], 1.41; 95% CI, 0.98 to 2.04) and OS (HR, 1.99; 95% CI, 1.27 to 3.13); 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS (HR, 1.94; 95% CI, 1.04 to 3.61) and OS (HR, 2.38; 95% CI, 1.04 to 5.41). There were no associations with EFS for the other NHL subtypes. Among patients with DLBCL and T-cell lymphoma, higher 1,25(OH)(2)D levels were associated with better EFS and OS, suggesting that any putative tumor 1-α-hydroxylase activity did not explain the 25(OH)D associations., Conclusion: 25(OH)D insufficiency was associated with inferior EFS and OS in DLBCL and T-cell lymphoma. Whether normalizing vitamin D levels in these patients improves outcomes will require testing in future trials.

Introduction: Vitamin D deficiency is common, but no data have been reported on vitamin D levels in light chain (AL) amyloidosis. Patients and Methods: In this exploratory study, stored serum samples from 173 patients with newly diagnosed AL amyloidosis were analyzed for vitamin studies which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). Measurements were made by liquid chromatography-tandem mass spectrometry. Kidney survival and overall survival (OS) were assessed in association to vitamin D status. Results: Cardiac and kidney involvement occurred in 69% and 63% of patients, respectively. 25(OH)D deficiency (<20 ng/mL) was seen in 56.6% of the patients and was notably found among patients with heavy proteinuria (96%), hypoalbuminemia (84.3%) and morbidly obese patients (68.3%). Heavy proteinuria (>5 gr/24-h) and vitamin D supplementation were independent predictors of 25(OH)D level on nominal multivariate regression analysis. 1,25(0H)2D deficiency was noted in 37.6% of patients and was independently associated with low eGFR and hypoalbuminemia. Progression to ESRD occurred in 23.7% of evaluable patients. Patients who progressed to ESRD had lower serum 25(OH)D and 1,25(OH)2D levels compared to those who did not progress to ESRD. On a multivariate analysis, severe 25(OH)D deficiency was an independent predictor of progression to ESRD as was renal stage, while 1,25(OH)2D deficiency was not. Conclusions: Hypovitaminosis D is common in AL amyloidosis, particularly among patients with heavy proteinuria. Severe 25(OH)D deficiency at time of diagnosis predicts progression to ESRD. [ABSTRACT FROM AUTHOR]

Vitamin D has long been recognized as a fundamental mediator of calcium and skeletal homeostasis. More recently, however, the important role that vitamin D plays in a wide variety of other cellular processes, including inhibition of carcinogenesis by induction of differentiation, inhibition of cellular proliferation and angiogenesis, and promotion of apoptosis, has been appreciated. Multiple myeloma, a severely debilitating, incurable, and uniformly fatal neoplastic disease of B cell origin, is frequently complicated by severe skeletal complications related to lytic bone destruction. The role that vitamin D may play in myeloma bone disease and/or multiple myeloma itself, however, has remained unknown. Here, we review our recent study of 148 subjects who had their vitamin D status determined within 2 weeks of a new clinical diagnosis of multiple myeloma. The prevalence of vitamin D deficiency (defined as a serum 25-hydroxyvitamin D level ,20 ng/mL (50 nmol/L)) increased in parallel with International Staging System categorization, indicating that subjects with worse clinical prognosis were more likely to have vitamin D deficiency. However, vitamin D levels were not predictive of skeletal morbidity. These data provide the first data demonstrating an inverse association between vitamin D status and clinical prognosis in patients with multiple myeloma. Further, these data suggest that assessment of vitamin D status may be an important adjunctive aspect of providing care for patients with myeloma, and that larger prospective studies to assess the role of vitamin D in multiple myeloma disease progression, overall survival, and quality of life may be warranted. [ABSTRACT FROM AUTHOR]