title: Soluble receptor for advanced glycation end products and risk of liver cancer.
abstract: Binding of advanced glycation end products (AGEs) to their receptor (RAGE) increases oxidative stress and inflammation and may be involved in liver injury and subsequent carcinogenesis. Soluble RAGE (sRAGE) may neutralize the effects mediated by the AGE/RAGE complex. Epidemiologic studies examining sRAGE or AGEs in association with liver cancer are lacking. We examined the associations between prediagnostic serum concentrations of sRAGE or Nϵ-(carboxymethyl)-lysine (CML)-AGE and hepatocellular carcinoma in a case-cohort study within a cohort of 29,133 Finnish male smokers who completed questionnaires and provided a fasting blood sample between 1985 and 1988. During follow-up beginning 5 years after enrollment through April 2006, 145 liver cancers occurred. Serum concentrations of sRAGE, CML-AGE, glucose, and insulin were measured in case subjects and 485 randomly sampled cohort participants. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) were available in most cases and in a subset of the study population. Weighted Cox proportional hazards regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) adjusted for age, years of smoking, and body mass index. sRAGE and CML-AGE concentrations were inversely associated with liver cancer. Further adjustment for glucose and insulin or exclusion of case subjects with chronic HBV or HCV did not change the associations.
  
  
  CONCLUSIONS
  Our results support the hypothesis that sRAGE is inversely associated with liver cancer. The findings need confirmation, particularly in populations that include women and nonsmokers. (HEPATOLOGY 2013 ).
authors: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. moyka@mail.nih.gov
authors: Kristin A
authors: KA
authors: Moy
authors: Li
authors: L
authors: Jiao
authors: Neal D
authors: ND
authors: Freedman
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Rashmi
authors: R
authors: Sinha
authors: Jarmo
authors: J
authors: Virtamo
authors: Demetrius
authors: D
authors: Albanes
authors: Rachael Z
authors: RZ
authors: Stolzenberg-Solomon
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000453:epidemiology; D005387:Finland / Q000453:epidemiology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000453:epidemiology; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012307:Risk Factors
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine