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

Created September 2023

There are 2 meta-analyses on this page

25-hydroxyvitamin D concentration is positively associated with overall survival in advanced pancreatic cancer: A systematic review and meta-analysis - 2023

Nutrition Research Vol 117, Sept 2023, Pages 73-82 https://doi.org/10.1016/j.nutres.2023.07.001 PDF is 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.

Introduction

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…

Discussion

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, …

Conclusion

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 titles of references

  • 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

40% less likely to die of Pancreatic Cancer if high vitamin D - meta-analyis Jan 2024

The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies

Eur J Nutr. 2024 Jan 3. doi: [10.1007/s00394-023-03302-w] PDF behind paywall

Yajing Shen 1 2, Junfen Xia 3, Chuncheng Yi 1 2, Tiandong Li 1 2, Peng Wang 1 2, Liping Dai 2 4, Jianxiang Shi 2 4, Keyan Wang 2 4, Changqing Sun 1 5, Hua Ye 6 7

Purpose: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach.

Methods: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs).

Results: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity.

Conclusion: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.

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VitaminDWiki – Cancer - Pancreatic category contains

{include}

81+ VitaminDWiki Cancer meta-analyses

This list is automatically updated

{LIST()}

Tags: Meta-analysis Pancreatic Cancer