Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort.
Grote VA., Kaaks R., Nieters A., Tjønneland A., Halkjær J., Overvad K., Skjelbo Nielsen MR., Boutron-Ruault MC., Clavel-Chapelon F., Racine A., Teucher B., Becker S., Pischon T., Boeing H., Trichopoulou A., Cassapa C., Stratigakou V., Palli D., Krogh V., Tumino R., Vineis P., Panico S., Rodríguez L., Duell EJ., Sánchez MJ., Dorronsoro M., Navarro C., Gurrea AB., Siersema PD., Peeters PH., Ye W., Sund M., Lindkvist B., Johansen D., Khaw KT., Wareham N., Allen NE., Travis RC., Fedirko V., Jenab M., Michaud DS., Chuang SC., Romaguera D., Bueno-de-Mesquita HB., Rohrmann S.
BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.