TY - JOUR
T1 - The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk
T2 - A Case-Control Study within the Prospective EPIC Cohort
AU - Grote, Verena A
AU - Nieters, Alexandra
AU - Kaaks, Rudolf
AU - Tjønneland, Anne
AU - Roswall, Nina
AU - Overvad, Kim
AU - Nielsen, Michael René Skjelbo
AU - Clavel-Chapelon, Françoise
AU - Boutron-Ruault, Marie Christine
AU - Racine, Antoine
AU - Teucher, Birgit
AU - Lukanova, Annekatrin
AU - Boeing, Heiner
AU - Drogan, Dagmar
AU - Trichopoulou, Antonia
AU - Trichopoulos, Dimitrios
AU - Lagiou, Pagona
AU - Palli, Domenico
AU - Sieri, Sabina
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Mattiello, Amalia
AU - Suárez, Marcial Vicente Argüelles
AU - Duell, Eric J
AU - Sánchez, María-José
AU - Dorronsoro, Miren
AU - Castaño, José María Huerta
AU - Barricarte, Aurelio
AU - Jeurnink, Suzanne M
AU - Peeters, Petra H M
AU - Sund, Malin
AU - Ye, Weimin
AU - Regner, Sara
AU - Lindkvist, Björn
AU - Khaw, Kay-Tee
AU - Wareham, Nick
AU - Allen, Naomi E
AU - Crowe, Francesca L
AU - Fedirko, Veronika
AU - Jenab, Mazda
AU - Romaguera, Dora
AU - Siddiq, Afshan
AU - Bueno-de-Mesquita, H Bas
AU - Rohrmann, Sabine
PY - 2012/4
Y1 - 2012/4
N2 - 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. Cancer Epidemiol Biomarkers Prev; ©2012 AACR.
AB - 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. Cancer Epidemiol Biomarkers Prev; ©2012 AACR.
U2 - 10.1158/1055-9965.EPI-11-1139
DO - 10.1158/1055-9965.EPI-11-1139
M3 - Journal article
SN - 1055-9965
VL - 21
SP - 619
EP - 628
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
ER -