Mayén Ana-Lucia, Aglago Elom K, Knaze Viktoria, Cordova Reynalda, Schalkwijk Casper G, Wagner Karl-Heinz, Aleksandrova Krasimira, Fedirko Veronika, Keski-Rahkonen Pekka, Leitzmann Michael F, Katzke Verena, Srour Bernard, Schulze Matthias B, Masala Giovanna, Krogh Vittorio, Panico Salvatore, Tumino Rosario, Bueno-de-Mesquita Bas, Brustad Magritt, Agudo Antonio, Chirlaque López María Dolores, Amiano Pilar, Ohlsson Bodil, Ramne Stina, Aune Dagfinn, Weiderpass Elisabete, Jenab Mazda, Freisling Heinz
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
Int J Cancer. 2021 Apr 25;149(4):854-64. doi: 10.1002/ijc.33612.
Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, N -[carboxymethyl]lysine (CML), N -[1-carboxyethyl]lysine (CEL) and N -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR- = 0.87, 95% CI: 0.76-0.99, HR- = 0.84, 95% CI: 0.74-0.96 and HR- = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR- = 1.28, 95% CI: 1.05-1.56, HR- = 1.17; 95% CI: 0.96-1.40, HR- = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.
晚期糖基化终末产物（AGEs）可能因其促炎和促氧化特性而导致肝癌发生。饮食是AGEs的主要来源，但关于AGEs摄入在肝癌病因学中的作用，人类证据稀少。我们在欧洲癌症与营养前瞻性调查队列（n = 450111）中研究了饮食中AGEs与肝胆癌风险之间的关联。使用与AGEs数据库相关联的特定国家饮食问卷估计了三种AGEs（N - [羧甲基]赖氨酸（CML）、N - [1 - 羧乙基]赖氨酸（CEL）和N - [5 - 羟基 - 5 - 甲基 - 4 - 咪唑啉 - 2 - 基] - 鸟氨酸（MG - H1））的饮食摄入量。使用多变量Cox比例风险回归估计饮食中AGEs与肝细胞癌（HCC）、胆囊癌和胆管癌风险之间关联的病因特异性风险比（HR）及其95%置信区间（CI）。在中位随访时间14.9年后，确定了255例HCC病例、100例胆囊癌病例和173例胆管癌病例。饮食中AGEs摄入量较高与HCC风险呈负相关（每增加1个标准差，HR = 0.87，95% CI：0.76 - 0.99，HR = 0.84，95% CI：0.74 - 0.96，HR = 0.84，95% CI：0.74 - 0.97）。相反，观察到与胆囊癌风险呈正相关（每增加1个标准差，HR = 1.28，95% CI：1.05 - 1.56，HR = 1.17；95% CI：0.96 - 1.40，HR = 1.27，95% CI：1.06 - 1.54）。肝内和肝外胆管癌未观察到关联。我们的研究结果表明，饮食中AGEs摄入量较高与HCC风险呈负相关，与胆囊癌风险呈正相关。
