Article

Soluble receptor for advanced glycation end products and risk of liver cancer

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Nation Institutes of Health, Bethesda, Maryland. .
Hepatology (Impact Factor: 11.19). 06/2013; 57(6). DOI: 10.1002/hep.26264
Source: PubMed

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 AGEs/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 (HCC) in a case-cohort study within a cohort of 29,133 Finnish male smokers who completed questionnaires and provided a fasting blood sample in 1985-1988. 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 cases and 485 randomly sampled cohort participants. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) were available on most cases and 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 (sRAGE: RR, highest versus lowest tertile, 0.77; 95% CI, 0.48-1.24; P(trend) =0.28; 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; P(trend) <0.0001; 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. Conclusion: Our results support the hypothesis that sRAGE is inversely associated with liver cancer. The findings need confirmation, particularly in populations that include women and non-smokers. (HEPATOLOGY 2013.).

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