The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort.
Grote VA., Nieters A., Kaaks R., Tjønneland A., Roswall N., Overvad K., Nielsen MR., Clavel-Chapelon F., Boutron-Ruault MC., Racine A., Teucher B., Lukanova A., Boeing H., Drogan D., Trichopoulou A., Trichopoulos D., Lagiou P., Palli D., Sieri S., Tumino R., Vineis P., Mattiello A., Argüelles Suárez MV., Duell EJ., Sánchez MJ., Dorronsoro M., Huerta Castaño JM., Barricarte A., Jeurnink SM., Peeters PH., Sund M., Ye W., Regner S., Lindkvist B., Khaw KT., Wareham N., Allen NE., Crowe FL., Fedirko V., Jenab M., Romaguera D., Siddiq A., Bueno-de-Mesquita HB., Rohrmann S.
BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). RESULTS: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). CONCLUSIONS AND IMPACT: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.