Vitamin D insufficiency and prognosis in non-Hodgkin's lymphoma.

College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Journal of Clinical Oncology (Impact Factor: 17.88). 09/2010; 28(27):4191-8. DOI: 10.1200/JCO.2010.28.6674
Source: PubMed

ABSTRACT 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.
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.
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.
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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Vitamin D has recently attracted attention because reduced levels are associated with the prevalence and aggressiveness of several cancers. The study aimed to evaluate the relationship between preoperative serum 25 hydroxyvitamin D [25(OH) vitamin D] levels and clinicopathologic characteristics in female patients with papillary thyroid cancer (PTC). Methods: A total of 548 female patients who underwent total thyroidectomy for PTC from June 2012 to May 2013 were included. Blood samples were obtained within 2 weeks prior to surgery. Patients were categorized into 4 quartiles by preoperative serum 25(OH) vitamin D levels. The clinicopathologic features of PTC were analyzed retrospectively. Results: Preoperative 25(OH) vitamin D was significantly lower in patients with a tumor size of >1 cm (P = 0.041) or lymph node metastasis (LNM; P = 0.043). No significant trends in several clinicopathologic features were observed in relation to increasing serum vitamin D concentrations except decreasing tumor size (P = 0.010). Patients in the 2nd quartile had a greater occurrence of T stage 3/4 [odds ratio (OR), 2.03; 95% confidence interval (CI): 1.19-3.44; P = 0.009)], LNM (OR, 2.03; 95% CI: 1.19-3.44; P = 0.009), lateral LNM (OR, 5.03; 95% CI: 1.66-15.28; P = 0.004), and extrathyroidal extension (ETE; OR, 1.95; 95% CI: 1.15-3.29; P = 0.013) than those in the 4th quartile. Multivariate analysis showed patients in the 2nd quartile had a greater occurrence of T stage 3/4 (OR, 1.89; 95% CI: 1.08-3.30; P = 0.026), LNM (OR, 2.04; 95% CI: 1.20-3.47; P = 0.009), lateral LNM (OR, 5.12; 95% CI: 1.68-15.59; P = 0.004), and ETE (OR, 1.81; 95% CI: 1.04-3.15; P = 0.036) than those in the 4th quartile. When the subjects were recategorized into 2 groups by median 25(OH) vitamin D levels, those with values below the median had a significantly higher risk of T stage 3/4, LNM, lateral LNM, stage III/IV, and ETE. All values except ETE sustained significance after adjustment. Conclusion: Lower preoperative serum 25(OH) vitamin D levels appear to be associated with poor clinicopathologic features in female patients with PTC.
    Thyroid: official journal of the American Thyroid Association 08/2014; · 2.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The GRCh37.p13 primary assembly of the human genome contains 20805 protein coding mRNA, and 37147 non-protein coding genes and pseudogenes that as a result of RNA processing and editing generate 196501 gene transcripts. Given the size and diversity of the human transcriptome, it is timely to revisit what is known of VDR function in the regulation and targeting of transcription. Early transcriptomic studies using microarray approaches focused on the protein coding mRNA that were regulated by the VDR, usually following treatment with ligand. These studies quickly established the approximate size, and surprising diversity of the VDR transcriptome, revealing it to be highly heterogenous and cell type and time dependent. With the discovery of microRNA, investigators also considered VDR regulation of these non-protein coding RNA. Again, cell and time dependency has emerged. Attempts to integrate mRNA and miRNA regulation patterns are beginning to reveal patterns of co-regulation and interaction that allow for greater control of mRNA expression, and the capacity to govern more complex cellular events. As the awareness of the diversity of non-coding RNA increases, it is increasingly likely it will be revealed that VDR actions are mediated through these molecules also. Key knowledge gaps remain over the VDR transcriptome. The causes for the cell and type dependent transcriptional heterogenetiy remain enigmatic. ChIP-Seq approaches have confirmed that VDR binding choices differ very significantly by cell type, but as yet the underlying causes distilling VDR binding choices are unclear. Similarly, it is clear that many of the VDR binding sites are non-canonical in nature but again the mechanisms underlying these interactions are unclear. Finally, although alternative splicing is clearly a very significant process in cellular transcriptional control, the lack of RNA-Seq data centered on VDR function are currently limiting the global assessment of the VDR transcriptome. VDR focused research that complements publically available data (e.g., ENCODE Birney et al., 2007; Birney, 2012), TCGA (Strausberg et al., 2002), GTEx (Consortium, 2013) will enable these questions to be addressed through large-scale data integration efforts.
    Frontiers in Physiology 05/2014; 5:181.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our results in an independent cohort of patients from France.
    Journal of Clinical Oncology 09/2014; · 17.88 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014