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 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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ABSTRACT: Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs), receptors for advanced glycation end products (RAGE), negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1) and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.Mediators of Inflammation 12/2014; 2014:251451. · 2.42 Impact Factor
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ABSTRACT: Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: -373.77 to -70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = -87.62; 95 % CI: -138.60 to -36.63; P = 0.001) with improved heterogeneity (I (2) = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = -231.34; 95 % CI: -450.10 to -12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: -67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function.Tumor Biology 05/2014; · 2.84 Impact Factor
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ABSTRACT: The role of diet in hepatocellular carcinoma (HCC) and its typical precursor, chronic liver disease (CLD), is poorly understood. Following dietary recommendations has been shown to reduce risk of many cancers, but whether such diets are associated with HCC and CLD is unknown. We prospectively evaluated the association of two dietary indices, the Healthy Eating Index-2010 (HEI-2010) and the alternate Mediterranean Diet Score (aMED), with HCC incidence and CLD mortality in a large U.S. prospective cohort. We calculated the HEI-2010 and aMED scores for 494,942 participants in the National Institutes of Health-AARP Diet and Health study, based on typical diet assessed using a food frequency questionnaire between 1995 and 1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of each index were estimated using Cox proportional hazards regression, after adjusting for alcohol intake, smoking, body mass index, diabetes, and other covariates. A total of 509 HCC cases (1995-2006) and 1053 CLD deaths (1995-2011) were documented during follow-up. Higher HEI-2010 scores, reflecting favorable adherence to dietary guidelines, were associated with lower risk of HCC (HR: 0.72, 95% CI: 0.53-0.97 for the highest quintile compared to lowest; P-trend=0.03), and lower mortality due to CLD (HR: 0.57; 95% CI: 0.46-0.71; P-trend<0.0001). High aMED scores were also associated with lower risk of HCC (HR: 0.62; 95% CI: 0.47-0.84; P-trend=0.0002) and lower risk of CLD mortality (HR: 0.52; 95% CI: (0.42-0.65; P-trend<0.0001). Conclusions: Adhering to dietary recommendations may reduce the risk of developing HCC and dying of CLD. (Hepatology 2014)Hepatology 04/2014; 60(2). · 11.19 Impact Factor