Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Hepatology. 2013 Jun;57(6):2338-45. doi: 10.1002/hep.26264. Epub 2013 May 14.
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.
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 ).
探讨可溶性晚期糖基化终产物受体（sRAGE）与肝癌的关系。
我们在一项队列研究中对 29133 名芬兰男性吸烟者进行了病例-队列研究，这些吸烟者在 1985 年至 1988 年期间完成了问卷调查并提供了空腹血样。在入组后 5 年开始直至 2006 年 4 月进行随访期间，发生了 145 例肝癌。在病例组和 485 名随机抽样的队列参与者中测量了 sRAGE、CML-AGE、葡萄糖和胰岛素的血清浓度。在大多数病例和研究人群的亚组中均获得了慢性乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染的信息。采用加权 Cox 比例风险回归计算了调整年龄、吸烟年限和体重指数后相对危险度（RR）和 95%置信区间（CI）。
sRAGE 和 CML-AGE 浓度与肝癌呈负相关。进一步调整葡萄糖和胰岛素或排除慢性 HBV 或 HCV 的病例组，并未改变这些关联。
我们的结果支持 sRAGE 与肝癌呈负相关的假说。这些发现需要进一步证实，特别是在包括女性和非吸烟者的人群中。
