Louise S Rasmussen1, Mette K Yilmaz2, Ursula G Falkmer3, Laurids Ø Poulsen3, Martin Bøgsted4, Heidi S Christensen4, Stig E Bojesen5, Benny V Jensen6, Inna M Chen6, Astrid Z Johansen6, Carsten P Hansen7, Jane P Hasselby8, Niels Holländer9, Svend E Nielsen10, Fahimeh Andersen11, Jon K Bjerregaard12, Per Pfeiffer13, Julia S Johansen14. 1. Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark. Electronic address: loskr@rn.dk. 2. Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark. 3. Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark. 4. Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark; Department of Haematology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark. 5. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. 7. Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 8. Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 9. Department of Oncology, Zealand University Hospital, Næstved, Denmark. 10. Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Oncology and Palliative Care, North Zealand University Hospital, Hillerød, Denmark. 11. Department of Oncology and Palliative Care, North Zealand University Hospital, Hillerød, Denmark. 12. Department of Oncology, Odense University Hospital, Odense, Denmark. 13. Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 14. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
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.
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.
Authors: James Bernard Walsh; Daniel M McCartney; Éamon Laird; Kevin McCarroll; Declan G Byrne; Martin Healy; Paula M O'Shea; Rose Anne Kenny; John L Faul Journal: Front Pharmacol Date: 2022-03-04 Impact factor: 5.810