Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Duijnhoven, Fränzel J.B. van; Jenab, Mazda; Hveem, Kristian; Siersema, Peter D.; Fedirko, Veronika; Duell, Eric J.; Kampman, Ellen; Halfweeg, Anouk; Kranen, Henk J. van; Ouweland, Jody M.W. van den; Weiderpass, Elisabete; Murphy, Neil; Langhammer, Arnulf; Ness-Jensen, Eivind; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Cadeau, Claire; Kvaskoff, Marina; Boutron-Ruault, Marie Christine; Katzke, Verena A.; Kühn, Tilman; Boeing, Heiner; Trichopoulou, Antonia; Kotanidou, Anastasia; Kritikou, Maria; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Panico, Salvatore; Matullo, Giuseppe; Peeters, Petra; Brustad, Magritt; Olsen, Karina Standahl; Lasheras, Cristina; Obón-Santacana, Mireia; Sánchez, María José; Dorronsoro, Miren; Chirlaque, Maria Dolores; Barricarte, Aurelio; Manjer, Jonas; Almquist, Martin; Renström, Frida; Ye, Weimin; Wareham, Nick; Khaw, Kay Tee; Bradbury, Kathryn E.; Freisling, Heinz; Aune, Dagfinn; Norat, Teresa; Riboli, Elio; Bueno-de-Mesquita, H.B.


Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.