Highlights
- •Pre-treatment vitamin D was associated with inflammatory biomarkers in PDAC.
- •Vitamin D deficiency was associated with increased levels of IL-6, YKL-40 and CRP.
- •Vitamin D deficiency yielded a short survival in patients with early stage.
- •Vitamin D deficiency did not influence survival in patients with advanced stage.
Abstract
Background
Vitamin D deficiency and inflammation are associated with increased mortality. We
investigated the relationship between pre-treatment serum vitamin D levels, inflammatory
biomarkers (IL-6, YKL-40 and CRP) and overall survival (OS) in pancreatic ductal adenocarcinoma
(PDAC) patients.
Methods
Pre-treatment serum vitamin D, IL-6, YKL-40 and CRP levels were determined in 1,267
patients with PDAC enrolled from July 2008 to September 2018 in the prospective BIOPAC
study (NCT03311776). The patients were grouped according to vitamin D levels: sufficient
>50 nmol/L, insufficient 25–50 nmol/L and deficient <25 nmol/L.
Results
Across all tumour stages, vitamin D-deficient patients had the highest median levels
of IL-6 (8.3 pg/mL, range 0.7–91), YKL-40 (177 ng/ml, range 25–5279) and CRP (15.5 mg/L,
range 0.8–384). The resected stage I and II patients with vitamin D deficiencies had
a shorter median OS, 18.3 months (95% CI, 12.1–31.5 months) than those with sufficient
levels, 29.7 months (95% CI, 22.3–36.1 months), and the hazard ratio for death was
1.55 (95% CI, 1.04–2.31; p = 0.03). In advanced PDAC, there was no significant difference in OS between the
vitamin D groups.
Conclusions
Vitamin D deficiency was associated with increased inflammatory biomarkers in all
PDAC stages. The resected stage I and II patients with sufficient vitamin D levels
had a higher OS than those with a vitamin D deficiency. However, there was no correlation
between vitamin D levels and survival in advanced PDAC. Future studies need to investigate
vitamin D supplementation effects on survival in PDAC.
Keywords
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References
- Pancreatic cancer.Nat Rev Dis Prim. 2016; 2: 1-23https://doi.org/10.1038/nrdp.2016.22
- Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.Cancer Res. 2014; 74: 2913-2921https://doi.org/10.1158/0008-5472.CAN-14-0155
- Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018.Eur J Cancer. 2018; 103: 356-387https://doi.org/10.1016/j.ejca.2018.07.005
- Hallmarks of cancer: the next generation.Cell. 2011; 144: 646-674https://doi.org/10.1016/j.cell.2011.02.013
- Systematic literature review of IL-6 as a biomarker or treatment target in patients with gastric, bile duct, pancreatic and colorectal cancer.Oncotarget. 2018; 9: 29820-29841https://doi.org/10.18632/oncotarget.25661
- Prognostic value of combined detection of serum interleukin-6, YKL-40, and C-reactive protein in patients with unresectable pancreatic cancer.Cancer Epidemiol Biomarkers Prev. 2019; 29: 176-184https://doi.org/10.1158/1055-9965.EPI-19-0672
- Roles of chitinase 3-like 1 in the development of cancer, neurodegenerative diseases, and inflammatory diseases.Pharmacol Ther. 2019; 203: 107394https://doi.org/10.1016/j.pharmthera.2019.107394
- Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies.Cancer Cell Int. 2019; 19: 259https://doi.org/10.1186/s12935-019-0983-y
- Putting cardiovascular disease and vitamin D insufficiency into perspective.Br J Nutr. 2005; 94: 483-492https://doi.org/10.1079/BJN20051544
- 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level.Cytokine. 1992; 4: 506-512https://doi.org/10.1016/1043-4666(92)90012-g
- 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes.Eur J Endocrinol. 2001; 145: 351-357https://doi.org/10.1530/eje.0.1450351
- Vitamin D receptor is expressed in pancreatic cancer cells and a vitamin D3 analogue decreases cell number.Pancreatology. 2003; 3: 41-46https://doi.org/10.1159/000069149
- Anti-growth effect of 1,25-dihydroxyvitamin D3-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside in pancreatic cancer cells.Anticancer Res. 2010; 30 (30/6/1875 [pii]): 1875-1880
- 19-nor-1α,25-Dihydroxyvitamin D 2 (Paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo.Cancer Biol Ther. 2008; 7: 430-436https://doi.org/10.4161/cbt.7.3.5418
- Retrospective analysis of the influence of 25-hydroxyvitamin D on disease progression and survival in pancreatic cancer.Nutr J. 2016; 15: 17https://doi.org/10.1186/s12937-016-0135-3
- Prediagnostic plasma 25-hydroxyvitamin D and pancreatic cancer survival.J Clin Oncol. 2016; 34: 2899-2905https://doi.org/10.1200/JCO.2015.66.3005
BIOmarkers in patients with Pancreatic Cancer (BIOPAC). https://www.herlevhospital.dk/BIOPAC/Sider/default.aspx Accesed on 18 June 2020.
- Prognostic impact of Charlson's Age-Comorbidity Index and other risk factors in patients with pancreatic cancer.Eur J Cancer Care. 2020; 29 (Engl)e13219https://doi.org/10.1111/ecc.13219
- National clinical guidelines.2015 (Danish)http://dpcg.gicancer.dk/Default.aspx?pID1/422Date accessed: June 18, 2020
- Validation of a combined comorbidity index.J Clin Epidemiol. 1994; 47: 1245-1251https://doi.org/10.1016/0895-4356(94)90129-5
- TNM classification of malignant tumours.ed 7. International Union Against Cancer (UICC), New York2009
- Vitamin D and pancreatic cancer.Cancer Lett. 2015; 368: 1-6https://doi.org/10.1016/j.canlet.2015.06.030
- Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON® automated analyzer.Clin Biochem. 2004; 37: 867-874https://doi.org/10.1016/j.clinbiochem.2004.06.006
- Vitamin D deficiency.N Engl J Med. 2007; 357: 266-281https://doi.org/10.1056/NEJMra070553
- Which circulating level of 25-hydroxyvitamin D is appropriate?.J Steroid Biochem Mol Biol. 2004; 89–90: 611-614https://doi.org/10.1016/j.jsbmb.2004.03.040
- Vitamin D deficiency.2010 (Danish)
- Pre-analytical and biological variability in circulating interleukin 6 in healthy subjects and patients with rheumatoid arthritis.Biomarkers. 2008; 13: 59-78https://doi.org/10.1080/13547500701615017
- Plasma YKL-40 levels in healthy subjects from the general population.Clin Chim Acta. 2011; 412: 709-712https://doi.org/10.1016/j.cca.2011.01.022
- Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration.PLoS Med. 2012; 9e1001216https://doi.org/10.1371/journal.pmed.1001216
- Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease.Am J Clin Nutr. 2004; 80: 1678S-1688Shttps://doi.org/10.1093/ajcn/80.6.1678S
- Vitamin D deficiency is associated with inflammation in older Irish adults.J Clin Endocrinol Metab. 2014; 99: 1807-1815https://doi.org/10.1210/jc.2013-3507
- Vitamin D-rich marine Inuit diet and markers of inflammation – a population-based survey in Greenland.J Nutr Sci. 2015; 4: e40https://doi.org/10.1017/jns.2015.33
- Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis.Oncotarget. 2017; 8: 64395-64406https://doi.org/10.18632/oncotarget.18888
- The vitamin D analog, MART-10, represses metastasis potential via downregulation of epithelial–mesenchymal transition in pancreatic cancer cells.Cancer Lett. 2014; 354: 235-244https://doi.org/10.1016/j.canlet.2014.08.019
High-dose Vitamin D3 in Pancreas Cancer (VITdCUT) https://clinicaltrials.gov/ct2/show/NCT03472833?te Accesed on 18 June 2020.
- A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer.Br J Cancer. 2002; 86: 680-685https://doi.org/10.1038/sj.bjc.6600162
- FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.N Engl J Med. 2011; 364: 1817-1825https://doi.org/10.1056/NEJMoa1011923
- Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.N Engl J Med. 2013; 369: 1691-1703https://doi.org/10.1056/NEJMoa1304369
Article Info
Publication History
Published online: December 17, 2020
Accepted:
October 30,
2020
Received:
August 19,
2020
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Letter re: Pre-treatment serum vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancer: Analysis of the prognostic effect of serum vitamin D on pancreatic cancer: Several confoundersEuropean Journal of CancerVol. 158
- PreviewWith great interest, we read the paper entitled ‘Pre-treatment serum vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancer’ by Rasmussen et al. [1], which investigated the correlations between pre-treatment serum vitamin D levels and serum inflammatory markers and survival in patients with pancreatic cancer. The findings suggested that vitamin D deficiency was associated with elevated markers of inflammation in all pancreatic cancer stages.
- Full-Text
- Preview
- Response to the letter entitled: Re: Pre-treatment serum vitamin D deficiency is associated with increased inflammatory biomarkers and short overall survival in patients with pancreatic cancer: Analysis of the prognostic effect of serum vitamin D on pancreatic cancer: Several confoundersEuropean Journal of CancerVol. 158
