Jiao Li, Stolzenberg-Solomon Rachael, Zimmerman Thea Palmer, Duan Zhigang, Chen Liang, Kahle Lisa, Risch Adam, Subar Amy F, Cross Amanda J, Hollenbeck Albert, Vlassara Helen, Striker Gary, Sinha Rashmi
From the Sections of Gastroenterology and Hepatology (LJ and LC) and Health Services Research (LJ, ZD, and LC), Department of Medicine, Baylor College of Medicine, Houston, TX; the Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics (RS-S and RS) and the Applied Research Program, Division of Cancer Control and Population Sciences (AFS), National Cancer Institute, NIH, Rockville, MD; Westat, Rockville, MD (TPZ); Information Management Services, Rockville, MD (LK and AR); the Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom (AJC); the Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, NY (HV and GS); and AARP, Washington, DC (AH).
Am J Clin Nutr. 2015 Jan;101(1):126-34. doi: 10.3945/ajcn.114.098061. Epub 2014 Nov 19.
Advanced glycation end products (AGEs) are a heterogeneous group of compounds present in uncooked foods as well as in foods cooked at high temperatures. AGEs have been associated with insulin resistance, oxidative stress, and chronic inflammation in patients with diabetes. Dietary AGEs are an important contributor to the AGE pool in the body. N(ϵ)-(carboxymethyl)lysine (CML) AGE is one of the major biologically and chemically well-characterized AGE markers. The consumption of red meat, which is CML-AGE rich, has been positively associated with pancreatic cancer in men.
With the use of a published food CML-AGE database, we estimated the consumption of CML AGE in the prospective NIH-AARP Diet and Health Study and evaluated the association between CML-AGE consumption and pancreatic cancer and the mediating effect of CML AGE on the association between red meat consumption and pancreatic cancer.
Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer.
During an average of 10.5 y of follow-up, we identified 2193 pancreatic cancer cases (1407 men and 786 women) from 528,251 subjects. With the comparison of subjects in the fifth and the first quintiles of CML-AGE consumption, we observed increased pancreatic cancer risk in men (HR: 1.43; 95% CI: 1.06, 1.93, P-trend = 0.003) but not women (HR: 1.14; 95% CI: 0.76, 1.72, P-trend = 0.42). Men in the highest quintile of red meat consumption had higher risk of pancreatic cancer (HR: 1.35; 95% CI: 1.07, 1.70), which attenuated after adjustment for CML-AGE consumption (HR: 1.20; 95% CI: 0.95, 1.53).
Dietary CML-AGE consumption was associated with modestly increased risk of pancreatic cancer in men and may partially explain the positive association between red meat and pancreatic cancer.
晚期糖基化终产物（AGEs）是一类异质性化合物，存在于未加工食品以及高温烹饪的食品中。AGEs与糖尿病患者的胰岛素抵抗、氧化应激和慢性炎症有关。膳食中的AGEs是体内AGE库的重要组成部分。N-ε-（羧甲基）赖氨酸（CML）AGE是主要的、生物学和化学特性明确的AGE标志物之一。食用富含CML-AGE的红肉与男性胰腺癌呈正相关。
利用已发表的食物CML-AGE数据库，我们在前瞻性的美国国立卫生研究院-美国退休人员协会饮食与健康研究中估算了CML AGE的摄入量，并评估了CML-AGE摄入量与胰腺癌之间的关联以及CML AGE在红肉摄入量与胰腺癌关联中的中介作用。
采用多变量Cox比例风险回归模型来估计胰腺癌的风险比（HR）和95%置信区间（CI）。
在平均10.5年的随访期间，我们从528,251名受试者中确定了2193例胰腺癌病例（1407名男性和786名女性）。比较CML-AGE摄入量处于第五分位数和第一分位数的受试者，我们观察到男性患胰腺癌的风险增加（HR：1.43；95%CI：1.06，1.93，P趋势 = 0.003），而女性未增加（HR：1.14；95%CI：0.76，1.72，P趋势 = 0.42）。红肉摄入量处于最高五分位数的男性患胰腺癌的风险更高（HR：1.35；95%CI：1.07，1.70），在调整CML-AGE摄入量后风险降低（HR：1.20；95%CI：0.95，1.53）。
膳食中CML-AGE的摄入与男性患胰腺癌的风险适度增加有关，并且可能部分解释了红肉与胰腺癌之间的正相关关系。
