@article{1b7a6b2852fd4029b5eb57b5e6a54e1e,
title = "Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.",
keywords = "Obesity, Pancreatic cancer, Prevention, Review, Type 2 diabetes mellitus",
author = "{Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer} and Guido Eibl and Zobeida Cruz-Monserrate and Murray Korc and Petrov, {Maxim S.} and Goodarzi, {Mark O.} and Fisher, {William E.} and Aida Habtezion and Aurelia Lugea and Pandol, {Stephen J.} and Hart, {Phil A.} and Andersen, {Dana K.}",
note = "Funding Information: Although the risk factors promoting PDAC development have been known for several decades, their underlying molecular mechanisms and interactions have just recently begun to be explored. High-quality epidemiologic studies associate obesity with an elevated risk of PDAC. Nevertheless, it is currently unclear whether so-called metabolically healthy obesity also carries an increased risk of PDAC. In addition, the beneficial effects of weight reduction and bariatric surgery on improving insulin resistance are known, but their role in decreasing PDAC incidence is still essentially unknown. Although the general pathways linking obesity and T2DM to PDAC have been described, including chronic tissue and systemic inflammation, cytokines/adipokines, hyperinsulinemia, and elevated IGF-1, the exact molecular and signaling pathways and their intricate interaction are still underexplored. Adipose tissue plays a central role in obesity and T2DM. However, the precise contribution and molecular signals of different adipose tissue depots and possible sex differences on PDAC development are not known. Several genetically engineered animal models are now available to study early PDAC development and risk factors and to investigate preventive strategies. Diet-induced obesity models are valuable tools to explore the role of obesity and metabolic disturbances in PDAC. However, very few studies exist that comprehensively investigate and compare the effects of individual nutrition components on PDAC development. It is currently unknown whether obesity experimentally induced by a high-fat or high-carbohydrate diet differs in increasing PDAC incidence or whether the simply increased caloric intake is the essential component. Altogether, given the high mortality of PDAC and expected increase in obesity and diabetes over the next few decades, efforts should be undertaken to mechanistically understand the link between obesity, diabetes, and PDAC. Preclinical animal models are available that will facilitate the study of these important interactions to advance our knowledge, so that the obesity- and diabetes-driven burden of PDAC can be curbed. The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer is a multicenter program jointly sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute that is pursuing a variety of studies to further identify mechanisms and biomarkers of PDAC to increase early detection of the disease and to inform intervention strategies. 188 Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer investigators are applying lessons learned from studies such as those described here to gain insights into the mechanisms by which diabetes and inflammation contribute to the incidence of PDAC. Z. Cruz-Monserrate is an assistant professor, Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, and Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus. M. Korc is a professor, Departments of Medicine, Biochemistry, and Molecular Biology, Division of Endocrinology, Indiana University School of Medicine, the Melvin and Bren Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indianapolis. M. S. Petrov is a senior lecturer, Department of Surgery, University of Auckland, Auckland, New Zealand. M. O. Goodarzi is a professor, Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA. W. E. Fisher is a professor, Department of Surgery, Baylor College of Medicine, Houston, TX. A. Habtezion is an assistant professor, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA. A. Lugea is an adjunct associate professor, Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, and Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles. S. J. Pandol is a professor, Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, and Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles. P. A. Hart is an assistant professor of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus. D. K. Andersen is program director, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Publisher Copyright: {\textcopyright} 2018 Academy of Nutrition and Dietetics",
year = "2018",
month = apr,
doi = "10.1016/j.jand.2017.07.005",
language = "English (US)",
volume = "118",
pages = "555--567",
journal = "Journal of the Academy of Nutrition and Dietetics",
issn = "2212-2672",
publisher = "Elsevier USA",
number = "4",
}