Advanced glycation end products, soluble receptor for advanced glycation end products and risk of liver cancer

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NCI	EPID-17

Authors

• K.A. Moy
• L. Jiao
• N.D. Freedman
• S.J. Weinstein
• R. Sinha
• J. Virtamo
• D. Albanes
• R.Z. Stolzenberg-Solomon

Abstract

Binding of advanced glycation end products (AGEs) to their receptor (RAGE) increases oxidative stress and inflammation in the liver. Soluble RAGE (sRAGE) may mitigate effects of RAGE activation. We examined associations between prediagnostic serum concentrations of sRAGE or Nε-(carboxymethyl)-lysine (CML)-AGE and liver cancer in a case-cohort study within a cohort of 29,133 Finnish male smokers who donated fasting blood in 1985-1988. During follow-up through April 2006, 145 liver cancers occurred. Serum concentrations of sRAGE, CML-AGE, glucose, and insulin were measured in cases and 485 randomly sampled cohort participants. Chronic hepatitis B (HBV) and hepatitis C virus (HCV) were measured. Weighted Cox proportional hazards regression was used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusted for age, years smoking, and body mass index. sRAGE and CML-AGE concentrations were inversely associated with liver cancer (sRAGE: RR, highest versus lowest tertile, 0.77; 95% CI, 0.48-1.24; continuous RR, 0.86; 95% CI, 0.75-0.99; CML-AGE: RR, highest versus lowest tertile, 0.19; 95% CI, 0.10-0.35; continuous RR, 0.74; 95% CI, 0.65-0.84). Further adjustment for glucose and insulin, or exclusion of cases with chronic HBV or HCV did not change the associations. Our results support the hypothesis that sRAGE may be protective against liver cancer.

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