The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort.
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
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.
Division of Cancer Epidemiology c020, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg, Germany.
Verena A
VA
Grote
Alexandra
A
Nieters
Rudolf
R
Kaaks
Anne
A
Tjønneland
Nina
N
Roswall
Kim
K
Overvad
Michael R Skjelbo
MR
Nielsen
Françoise
F
Clavel-Chapelon
Marie Christine
MC
Boutron-Ruault
Antoine
A
Racine
Birgit
B
Teucher
Annekatrin
A
Lukanova
Heiner
H
Boeing
Dagmar
D
Drogan
Antonia
A
Trichopoulou
Dimitrios
D
Trichopoulos
Pagona
P
Lagiou
Domenico
D
Palli
Sabina
S
Sieri
Rosario
R
Tumino
Paolo
P
Vineis
Amalia
A
Mattiello
Marcial Vicente
MV
Argüelles Suárez
Eric J
EJ
Duell
María-José
MJ
Sánchez
Miren
M
Dorronsoro
José María
JM
Huerta Castaño
Aurelio
A
Barricarte
Suzanne M
SM
Jeurnink
Petra H M
PH
Peeters
Malin
M
Sund
Weimin
W
Ye
Sara
S
Regner
Björn
B
Lindkvist
Kay-Tee
KT
Khaw
Nick
N
Wareham
Naomi E
NE
Allen
Francesca L
FL
Crowe
Veronika
V
Fedirko
Mazda
M
Jenab
Dora
D
Romaguera
Afshan
A
Siddiq
H Bas
HB
Bueno-de-Mesquita
Sabine
S
Rohrmann
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D011379:Prognosis; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine