title: Dietary consumption of advanced glycation end products and pancreatic cancer in the prospective NIH-AARP Diet and Health Study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Multivariate Cox proportional hazard regression models were used to estimate HRs and 95% CIs for pancreatic cancer.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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).
authors.forename: Li
authors.initials: L
authors.lastname: Jiao
authors.affiliation: 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).
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.affiliation: 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).
authors.forename: Thea Palmer
authors.initials: TP
authors.lastname: Zimmerman
authors.affiliation: 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).
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Duan
authors.affiliation: 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).
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: 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).
authors.forename: Lisa
authors.initials: L
authors.lastname: Kahle
authors.affiliation: 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).
authors.forename: Adam
authors.initials: A
authors.lastname: Risch
authors.affiliation: 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).
authors.forename: Amy F
authors.initials: AF
authors.lastname: Subar
authors.affiliation: 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).
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.affiliation: 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).
authors.forename: Albert
authors.initials: A
authors.lastname: Hollenbeck
authors.affiliation: 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).
authors.forename: Helen
authors.initials: H
authors.lastname: Vlassara
authors.affiliation: 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).
authors.forename: Gary
authors.initials: G
authors.lastname: Striker
authors.affiliation: 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).
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D004032:Diet / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis; D006801:Humans; D008239:Lysine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D008460:Meat / Q000009:adverse effects* / Q000032:analysis; D008875:Middle Aged; D016011:Normal Distribution; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012737:Sex Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
chemical_list: D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine
keywords: advanced glycation end products; diet; inflammation; pancreatic cancer; risk