Vasilis Vasiliou. Q. Max Guo. Alcohol and Cancer

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1 Alcohol and Cancer

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3 Samir Zakhari Editors Vasilis Vasiliou Q. Max Guo Alcohol and Cancer

4 Editors Samir Zakhari, Ph.D. Director Division of Metabolism and Health Effects National Institute on Alcohol Abuse and Alcoholism National Institutes of Health 5635 Fishers Lane, Room 2031 Bethesda, MD USA Vasilis Vasiliou, Ph.D. Professor and Director of Toxicology Graduate Program Department of Pharmaceutical Sciences University of Colorado Denver C238-P15 RC2, Room P East 19th Avenue Aurora, CO USA Q. Max Guo, Ph.D. Division of Metabolism and Health Effects National Institute on Alcohol Abuse and Alcoholism National Institutes of Health 5635 Fishers Lane, Room 2031 Bethesda, MD USA ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (

5 Preface Chronic alcohol consumption is a major health problem worldwide, and may lead to addiction and damage of almost every organ of the body. The World Health Organization (WHO) Global Burden of Disease has concluded that approximately 1.8 million people die each year due to alcohol (3.2% of all deaths). One of the most significant diseases caused by chronic alcohol consumption is cancer. According to the International Agency for Research on Cancer (IARC) in Lyon, France, alcohol is considered a carcinogen for the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and the female breast. Worldwide, a total of approximately 389,000 cases of these cancers representing 3.6% of all cancers (5.2% in men and 1.7% in women) are derived from chronic alcohol ingestion. The fact that alcohol causes cancer is not new. The first observation that alcohol is responsible for esophageal cancer was published by the French pathologist Lamu in Paris in It took a long time until 1978 when the National Institute of Health (NIH) organized a workshop on this topic due to the fact that more and more epidemiologic data appeared demonstrating the causal relationship between alcohol and certain types of cancer. However, at this time mechanisms of alcohol-mediated carcinogenesis were almost completely unknown. A second workshop in 2004 took into account the increasing literature on possible mechanisms by which ethanol and/or its first metabolite acetaldehyde stimulates carcinogenesis. The results of this workshop were published in ALCOHOL. A further step forward in bringing this important issue to the scientific public was the workshop held in Lyon at the IARC in February 2007 which ended in a clear statement that alcoholic beverages are carcinogenic and that acetaldehyde is a causal factor in esophageal carcinogenesis published in the April issue 2007 of LANCET ONCOLOGY. Considering this historic development, it was time for a more detailed look at the effect of alcohol on carcinogenesis in a broader perspective, including epidemiology, biochemistry as well as molecular and cell biology. On June 8 9, 2010, the Division of Metabolism and Health Effects of the National Institute of Alcoholism and Alcohol Abuse (NIAAA) has invited a panel of experts to discuss this important issue. As a result, Dr. Sam Zakhari and his colleagues presented a comprehensive v

6 vi Preface book on alcohol and cancer with major emphasis on molecular mechanisms, including the effect of alcohol metabolism on cancer, the effect of ethanol on epigenetics, intracellular signal pathways, retinoic acid metabolism, protein homeostasis, inflammation, immune surveillance, and stem cells. This book could have come at no better time. The contents of this book is carefully designed and analytically presented, summarizing an up-to-date knowledge on this topic with the most recent literature until summer The book Alcohol and Cancer edited by Sam Zakhari, Q. Max Guo, and Vasilis Vasiliou is a comprehensive and unique summary on a topic of general and specific interest to a broad readership, including oncologists, basic cancer researchers, gastroenterologists, hepatologists, and other specialists dealing with cancer. It will undoubtedly become an international landmark. Dr. Sam Zakhari works at the NIH since He is Director of the Division of Metabolism and Health Effects of the NIAAA,. He is an internationally well-known expert in the field of alcohol metabolism and alcohol associated toxicity, having worked in this field for decades. It is he and his coworkers who guarantee for the high standard and quality of this book. I wish to thank the authors for presenting an outstanding summary on a most important issue and I am convinced that this book receives the international recognition which it deserves. Heidelberg October, 2010 Helmut K. Seitz, MD, PhD, AGAF

7 Contents 1 Alcohol as a Human Carcinogen... 1 Philip J. Brooks 2 Cancer and Alcohol: An Overview of Tumorigenesis... 5 William C. Dunty Jr. 3 Alcohol and Cancer Epidemiology R. Thomas Gentry 4 Alcohol Metabolism and Its Implications for Cancer Gary J. Murray, Philip J. Brooks, and Samir Zakhari 5 Epigenetics, Alcohol, and Cancer Dale Hereld and Q. Max Guo 6 Alcohol, Cancer Genes, and Signaling Pathways William C. Dunty Jr. 7 Alcohol, Retinoic Acid, and Cancer Svetlana Radaeva 8 Alcohol, Altered Protein Homeostasis, and Cancer András Orosz 9 Alcohol and the Inflammatory Function of Immune Cells in Cancer Development H. Joe Wang 10 Immune Surveillance and Tumor Evasion M. Katherine Jung vii

8 viii Contents 11 Stem Cells and Alcohol-Related Cancers Zhigang (Peter) Gao and Q. Max Guo 12 Epilogue, Consensus Recommendations: Alcohol and Cancer Samir Zakhari Index

9 About the Contributors Phillip J. Brooks, Ph.D Neurobiology, University of North Carolina at Chapel Hill, 1990 Postdoc: Rockefeller University Started at NIH: 1994 William C. Dunty, Jr., PhD Cell and Developmental Biology, University of North Carolina at Chapel Hill, 2002 Postdoc: National Cancer Institute Started at NIH: 2003 ix

10 x About the Contributors Zhigang (Peter) Gao, MD Henan Medical University, 1988 Postdoc: Johns Hopkins School of Medicine Started at NIH: 2005 R. Thomas Gentry, PhD Behavioral Neuroendocrinology, Univ. of Massachusetts at Amherst, 1976 Postdoc: Rockefeller University Started at NIH: 1996 Q. Max Guo, PhD Biochemistry, RNA Splicing, Ohio State University, 1992 Postdoc: University of California at San Francisco Started at NIH: 2002

11 About the Contributors xi Dale Hereld, MD, PhD Biochemistry, Cell, and Molecular Biology; Johns Hopkins University, 1989 Postdoc: Johns Hopkins University Started at NIH: 2008 M. Katherine Jung, PhD Physiological Chemistry, Ohio State University, 1982 Postdoc: Friedrich Miescher Institute, Basel Started at NIH: 2007 Gary Murray, PhD Chemistry, University of Waterloo, Canada, 1977 Postdoc: National Institutes of Health Started at NIH: 1977

12 xii About the Contributors András Orosz, PhD Biochemistry and Molecular Biology, University of Szeged, Hungary, 1991 Postdoc: National Cancer Institute Started at NIH: 2008 Svetlana Radaeva, PhD Cell and Developmental Biology, Koltzov Institute, Russian Academy of Sciences, 1992 Postdoc: German Cancer Research Center, Heidelberg Started at NIH: 2000 H. Joe Wang, PhD Molecular Genetics, Ohio State University, 1994 Postdoc: University of California at San Francisco Started at NIH: 2007

13 About the Contributors xiii Samir Zakhari, PhD Pharmacology, Czechoslovak Academy of Sciences, 1975 Postdoc: University of Pennsylvania School of Medicine Started at NIH: 1986

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15 Contributors Phillip J. Brooks, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, William C. Dunty, Jr, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Zhigang (Peter) Gao, MD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, R. Thomas Gentry, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Q. Max Guo, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA Dale Hereld, MD, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, M. Katherine Jung, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Gary J. Murray, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, András Orosz, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA xv

16 xvi Contributors Svetlana Radaeva, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, H. Joe Wang, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA Samir Zakhari, PhD Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,