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Pancreatic Cancer survival 2.3 X more likely if good level of Vitamin D – meta-analysis Sept 2023

25-hydroxyvitamin D concentration is positively associated with overall survival in advanced pancreatic cancer: A systematic review and meta-analysis

Nutrition Research Vol 117, Sept 2023, Pages 73-82 https://doi.org/10.1016/j.nutres.2023.07.001 PDF behind a paywall
Jing Li a #, Haiyan Zhang a #, Hongda Zhu b, Zhu Dai a

Studies have shown that 25-hydroxyvitamin D (25(OH)D) is predictive of survival following a diagnosis of cancer. However, evidence of the relationship between 25(OH)D and the survival of patients with pancreatic cancer has been inconsistent. We hypothesized that circulating 25(OH)D concentrations may be positively correlated with better prognosis in advanced pancreatic cancer. PubMed, EMBASE, Cochrane Library, and Web of Science database entries through April 2023, along with the reference lists of related studies, were searched. Additionally, we extracted observational studies reporting the association between 25(OH)D concentrations and the outcome of interest (overall survival [OS]) in advanced pancreatic cancer patients aged 18 years or older. Ultimately, 7 articles involving 2369 patients were included in this systematic review and meta-analysis. The results indicated that 25(OH)D concentrations were positively correlated with OS (hazard ratio = 2.37; 95% confidence interval, 2.22–2.54; P < .001). No association was found between 25(OH)D and progression-free survival. There was significant heterogeneity between studies in terms of OS (I2 = 85.5%, P < .001). Our subgroup analysis revealed that this high heterogeneity may be attributed to the studies’ different regions, designs, sample sources, and detection methods of 25(OH)D. Additionally, Begg's and Egger's tests indicated the presence of publication bias. To our knowledge, this is the first meta-analysis to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer. Our results suggested that circulating 25(OH)D concentrations were positively correlated with OS, indicating that 25(OH)D may be a potential prognostic marker in advanced pancreatic cancer.

Graphical abstract
This systematic review and meta-analysis was performed to evaluate the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and survival outcomes among patients with advanced pancreatic cancer. The results showed that 25(OH)D concentrations were positively correlated with overall survival among patients with pancreatic cancer, indicating that 25(OH)D concentration may be a potential prognostic marker in advanced pancreatic cancer.

Pancreatic cancer is considered a fatal disease and is 1 of the most aggressive and deadly types of malignant tumors [1]. It has been reported that the 5-year survival rate of patients with pancreatic cancer varies in different regions and countries in the world; however, these rates have consistently remained below 10% [2]. This is partly because pancreatic cancer tends to metastasize to lymph nodes or distant sites at an early stage because of its high capacity for invasion and migration [3]. To date, except for the onset stage, there are few known patient characteristics or circulating markers that can predict the survival time of patients with pancreatic cancer.

The classical role of vitamin D (VD) is to maintain calcium homeostasis and help regulate bone metabolism [4]. Initially, it was considered to have autocrine and paracrine effects until the discovery that multiple cells throughout the body can express both vitamin D receptors (VDRs) and the hydroxylase necessary to produce calcitriol [5]. VD is predominantly synthesized from 7-dehydrocholesterol in the skin on exposure to sunlight, whereas the remaining VD is obtained from dietary sources. VD itself has low activity at physiological concentrations and requires 2 successive hydroxylation reactions. It is first metabolized by 25-hydroxylase (CYP2R1 and CYP27A1) to 25-hydroxyvitamin D (25(OH)D) in the liver. Notably, 25(OH)D is the primary circulating form of VD and a clinical marker. Subsequently, 25(OH)D is further metabolized by 1α-hydroxylase, mainly in the proximal tubule of the kidney, to 1α,25-dihydroxyvitamin D [6], the most biologically active form of VD. It can bind to VDRs that influence target genes involved in intracellular signaling pathways, including cell growth, differentiation, adhesion, and apoptosis [7]. This altered cellular mechanism plays a key role in cancer development and suggests a potential relationship between VD and cancer.

Multiple experimental studies have indicated that VD participates in pancreatic carcinogenesis and demonstrated the therapeutic potential of VD analogs via the engagement of VDRs in tumor and supportive cells within the tumor stroma [8,9]. Notably, an inverse association between serum 25(OH)D concentration and risk for cancer has been commonly reported in epidemiological studies [10]. Additionally, there is widespread interest in evaluating the association between circulating 25(OH)D and patient prognosis. Some clinical studies have revealed longer overall survival (OS) in patients with pancreatic cancer and sufficient 25(OH)D concentrations [11]. However, the results of this type of study were inconsistent with those of other studies, showing no significant relationship between circulating 25(OH)D concentrations and survival outcomes [12].

Therefore, to assess the effect of 25(OH)D on survival outcomes in advanced pancreatic cancer patients, we performed a systematic review and meta-analysis to evaluate the association between circulating 25(OH)D concentrations and OS. We hypothesized that 25(OH)D concentrations may be positively correlated with OS in advanced pancreatic cancer.

Section snippets

Literature search
We searched PubMed, EMBASE, Web of Science, and Cochrane library databases (on April 2023) for cohort studies assessing the association between circulating 25(OH)D concentrations and OS in patients with advanced pancreatic cancers. Medical Subject Headings including “Pancreatic Neoplasms” and “Vitamin D” were used to choose qualified studies, and these were further combined with keyword searches in titles and abstracts. Additionally, the references cited in all selected studies and published…

Study selection
A flowchart of the study retrieval process is shown in Fig. 1. A total of 2166 potential studies were identified from the initial search of the previously mentioned databases, of which 538 were duplicates. After removing duplicate records and screening the titles and abstracts, 846 records remained. The full-text documents of these records were assessed, resulting in the exclusion of 839 records. The exclusion criteria were as follows: (1) review articles (n = 445); (2) animal experiments (n…

This meta-analysis is the first to evaluate the association between 25(OH)D concentrations and OS among patients with pancreatic cancer and to assess the potential prognostic value of 25(OH)D. Our results supported the notion that a positive correlation existed between 25(OH)D and OS in patients with pancreatic cancer, which was consistent with our hypothesis.

Pancreatic cancer is a prevalent disease characterized by a low survival rate, primarily because it is often detected at advanced stages, …

In conclusion, our study indicated that 25(OH)D concentrations were positively correlated with OS, which may provide useful prognostic information for advanced pancreatic cancer patients. However, more studies are needed to validate this finding, and the mechanism behind the observation should be evaluated in further studies…

Some reference titles
  • Vitamin D and pancreatic cancer
  • Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications
  • Vitamin D for cancer prevention: global perspective
  • Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number
  • The vitamin D system is deregulated in pancreatic diseases
  • Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis
  • Relationships among body mass index, longitudinal body composition alterations, and survival in patients with locally advanced pancreatic cancer receiving chemoradiation: a pilot study
  • The vitamin D dose response in obesity
  • High prevalence of vitamin D deficiency in urban health checkup population
  • Vitamin D, parathyroid hormone, and cardiovascular events among older adults
  • Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in t 47d breast cancer cells
  • Evidence of sexual dimorphism in placental vitamin D metabolism: testosterone inhibits calcitriol-dependent cathelicidin expression
  • Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease
  • Current epidemiology of pancreatic cancer: challenges and opportunities
  • Pancreatic cancer: a review of epidemiology, trend, and risk factors
  • Pancreatic cancer: a review of current treatment and novel therapies
  • Vitamin D binding protein and bone health
  • Sex differences in vitamin D metabolism, serum levels and action
  • Calcipotriol targets lrp6 to inhibit wnt signaling in pancreatic cancer
  • Activation of vitamin D receptor signaling downregulates the expression of nuclear foxm1 protein and suppresses pancreatic cancer cell stemness
  • Vitamin D for the prevention and treatment of pancreatic cancer
  • Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival

VitaminDWiki – Cancer - Pancreatic category contains

55 items in Cancer-Pancreatic

All of the following decrease many cancers    Usually by prevention, but sometimes also by treatment
Vitamin D   Omega-3  Activators of Vitamin D Receptor   Magnesium  Vitamin K
   Suspect that the supplements are synergistic