Cancer Risks Strategies for Elimination Edited by Peter Bannasch With 34 Figures Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Prof. Dr. PETER BANNASCH lnstitut flir Experimentelle Pathologie Deutsches Krebsforschungszentrum 1m Neuenheimer Feld 280 D-6900 Heidelberg The publication of this book was supported by the Arbeitsgemeinschaft flir Grossforschungseinrichtungen (AGF). Institutions participating in the AGF-KoordinierungsausschuB Krebsforschung DKFZ Deutsches Krebsforschungszentrum Heidelberg GBF Gesellschaft flir Biotechnologische Forschung Braunschweig GSF Gesellschaft flir Strahl en-und Umweltforschung Neuherberg KF A Kernforschungsanlage Iiilich KfK Kernforschungszentrum Karlsruhe Library of Congress Cataloging-in-Publication Data. Cancer risks. Includes bibliographies and index. 1. Cancer - Prevention. 2. Carcinogens. 3. Carcinogenesis. 4. Health risk assessment. 1. Bannasch. Peter. [DNLM: 1. Carcinogens - toxicity. 2. Neoplasms - prevention & control. 3. Oncogenic Viruses - pathogenicity. QZ 202 C21564] RC268.C3676 1987 616.99'4052 87-4350 ISBN-13 978-3-540-17465-3 e-ISBN-13: 978-3-642-71843-4 DOl 10.1007/978-3-642-71843-4 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned. specifically the rights of translation, reprinting, reuse of illustrations, recitation, broad casting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9,1965, in its version of June 24,1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1987 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The pnblisher can give no guarantee for information about drug dosage and applica tion thereof contained in this book. In every individual case the respective user must check its ac curacy by consulting other pharmaceutical literature. Typesetting by, Petersche Druckerei GmbH & Co. Offset KG. Rothenburg ob del' Tauber 2121/3130-543210 Preface A large body of information about possible causes of cancer has been ac cumulated by both clinical experience in man and observations in animal experiments. There is general agreement that in most cases cancer is due to exogenous factors, albeit the genetic disposition may also play an impor tant part. Three main categories of exogenous risk factors have been iden tified, namely chemicals, radiation, and viruses. In principle, it should be possible to prevent cancer by eliminating such risk factors. However, in spite of the rapidly growing number of well established risk factors, many shortcomings in our understanding of the causes of human cancer and in the introduction of effective preventive measures are evident. In addition to obvious gaps in our scientific knowledge, inadequacies in personal life style, irresponsible handling of environmental contaminants, and in some areas also deficiencies in political decisions seriously hamper the elimina tion of risk factors for cancer. It was this background which prompted the Committee coordinating Cancer Research in the GroBforschungseinrichtungen in the Federal Re public of Germany to organize a conference on Strategies for the Elimina tion of Cancer Risks. The conference was held in Heidelberg in June 1986. In areas which appeared to be especially pertinent to public health, author itative speakers presented the state of the art and prepared the basis for the discussion. Both the presentations of the speakers and the summaries of the discussions are contained in this book. The idea of the conference emerged long before the atomic energy plant accident in Chemobyl and the severe chemical pollution of the river Rhine had happened. Some of the consequences of the Chemobyl accident were discussed at the conference. As to the chemical risk factors, in addi tion to occupational cancer, special emphasis was laid upon tobacco smok ing, one of the best known risk factors for cancer in man. The discussion on viruses as possible risk factors for human cancer aims at the develop ment of vaccines which might prevent certain types of cancer. I am obliged to all members of the Scientific Committee who gave valu able advice for the program of the conference: L. E. Feinendegen (Diissel dorflJiilich), W. Gassner (Munich), U.Hagen (Munich/Neuherberg), H. zurHausen (Heidelberg), P. Herrlich (Karlsruhe), P. Miihlradt (Braun schweig), R. Preussmann (Heidelberg), and D. Schmahl (Heidelberg). I am also grateful to the Administration of the German Cancer Research Center and to my coworkers, who guaranteed a smooth running of the VI Preface meeting. My special thanks go to the speakers, the moderators, and the rapporteurs of the discussions, and to all the participants who contributed to the success of the meeting and provided the basis for this book. Finally, I am indebted to Ute Heilmann of Springer-Verlag for excellent coopera tion and much support in achieving rapid publication of the proceedings. Heidelberg, December 5,1986 PETER BANNASCH Contents Session 1 General Aspects Chairman: F. VOGEL Genetic Predisposition for Cancer Risks in Man D.G.HARNDEN ................ . 3 The Role of Epidemiology in the Detection and Reduction of Cancer Risks R.DoLL ............. . 14 Summary of Discussion: Session 1 L. ARAB-KoHLMEIER ...... . 24 Session 2 Chemical Carcinogens: Risk Assessment Chairman: D.NEUBERT Assessment of Cancer Risk from Chemicals D. HENSCHLER 27 Validity of Short-Term Tests to Detect Carcinogenic Chemicals H.GREIM, V.ANDRAE, W. GOGGELMANN, L.SCHWARZ, and K. H. SUMMER (With 5 Figures) ............. 33 Preneoplastic Lesions as Indicators of the Carcinogenic Risk Caused by Chemicals P. BANNASCH, H. ENZMANN, and H. ZERBAN (With 6 Figures) 47 Carcinogenic Risk Assessment: Are Animals Good Surrogates for Man? I.F.H.PURCHASE ........ . 65 Summary of Discussion: Session 2 R.BAss ............. . 80 VIII Contents Session 3 Chemical Carcinogens: Primary Prevention Chairman: D.ScHMA.HL Possibilities of Primary Prevention Against Chemical Carcinogens R. PREUSSMANN (With 3 Figures) .................. 87 Primary Prevention Against Occupational Carcinogens P. J. LANDRIGAN and I. J. SELIKOFF . . . . . . . . . . . . 94 Chemical Carcinogens in Tobacco D. HOFFMANN, E. L. WYNDER, S. S. HECHT, K. D. BRUNNEMANN, E.J.LAVoIE, and N.J. HALEY (With 4 Figures) ........... 101 Primary Prevention of Tobacco-Related Cancer E. L. WYNDER and M. A. ORLANDI (With 6 Figures) ......... 114 Summary of Discussion: Session 3 H.-G. NEUMANN ........................... 133 Session 4 Physical Carcinogens Chairman: W. GassNER Cancer Risk from Ultraviolet Radiation H.IpPEN ................ . . ...... 137 Assessment of Cancer Risks Due to Ionizing Radiations A.M.KELLERER (With 1 Figure) ........ . ...... 143 Cancer Risk from Environmental Radioactivity W,JACOBI (With 5 Figures) ...................... 154 Summary of Discussion: Session 4 E.W.HAHN ........... . . .. 166 Session 5 Oncogenic Viruses Chairman: E. WECKER Viruses in Human Tumors H. zuRHAUSEN (With 1 Figure) ... 171 Strategies in the Prevention of Infections by Oncogenic Viruses F.DEINHARDT (With 3 Figures) .................... 181 Contents IX Summary of Discussion: Session 5 G. HUNSMANN . . . . . . . . . . . . ........ 190 Summary of Round Table Discussion on Strategies Against Tobacco Cancer G.ErSENBRAND .............•.....•........ 192 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 List of Contributors ANDRAE, ULRICH, Institut fur Toxikologie der Gesellschaft fur Strahlen und Umweltforschung, D-8042 Neuherberg, FRG ARAB-KoHLMEIER, LENORE, Bundesgesundheitsamt, Institut fur Sozialme dizin und Epidemiologie, Postfach 330013, D-1000 Berlin 33, FRG BANNASCH, PETER, Institut fur Experimentelle Pathologie, Deutsches Krebs forschungszentrum, 1m Neuenheimer Feld 280, D-6900 Heidelberg, FRG BASS, ROLF, Bundesgesundheitsamt, Thielallee 88-92, D-1000 Berlin 33, FRG BRUNNEMANN, KLAUS D., Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595, U.S.A. DEINHARDT, FRIEDRICH, Max von Pettenkofer Institut fur Hygiene und Me dizinische Mikrobiologie der Ludwig-Maximilians-Universitat Mun chen, Pettenkoferstr. 9, D-8000 Munchen 2, FRG DOLL, RICHARD, SIR, Imperial Cancer Research Fund, Cancer Epidemiol ogy Unit, Radcliffe Infirmary, Oxford OX2 6HE, U.K. EISENBRAND, GERHARD, Lebensmittelchemie und Umwelttoxikologie der Universitat Kaiserslautern, Erwin-Schrodinger-Str., D-6750 Kaisers lautern, FRG ENZMANN, HARALD, Institut fur Experimentelle Pathologie, Deutsches Krebsforschungszentrum, 1m Neuenheimer Feld 280, D-6900 Heidel berg, FRG GOGGELMANN, WALTRAUD, Institut fur Toxikologie der Gesellschaft fur Strahlen- und Umweltforschung, D-8042 Neuherberg, FRG GREIM, HELMUT, Institut fur Toxikologie der Gesellschaft fUr Strahlen-und Umweltforschung, D-8042 Neuherberg, FRG HAHN, ERIC W., Institut fUr Nuklearmedizin, Deutsches Krebsforschungs zentrum, 1m Neuenheimer Feld 280, D-6900 Heidelberg, FRG HALEY, NANCY J., Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595, U.S.A. XII List of Contributors HARNDEN, DAVID G., The Paterson Laboratories, Christie Hospital and Holt Radium Institute, Wilmslow Road, Manchester M20 9BX, U.K. HAUSEN ZUR, HARALD, Deutsches Krebsforschungszentrum, 1m Neuen heimer Feld 280, D-6900 Heidelberg, FRG HECHT, STEPHEN S., Naylor Dana Institute for Disease Prevention, Ameri can Health Foundation, Valhalla, NY 10595, U.S.A. HENSCHLER, DIETER, Institut fUr Pharmakologie und Toxikologie, Universi tat Wurzburg, Versbacher Landstr. 9, D-8700 Wurzburg, FRG HOFFMANN, DIETRICH, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595, U.S.A. HUNSMANN, GERHARD, Abteilung fUr Virologie und Immunologie, Deut sches Primatenzentrum, Kellnerweg 4, D-3400 Gottingen, FRG IpPEN, HELMUT, Abt. Dermatologie und Venerologie I, Universitats-Haut klinik, von Siebold-Str. 3, D-3400 Gottingen, FRG JAKOB!, WOLFGANG, GSF Neuherberg, Institut fUr Strahlenschutz, Ingol stadter Landstr. 1, D-8042 Neuherberg, FRG KELLERER, ALBRECHT M., Institut fUr Medizinische Strahlenkunde, Univer sitat Wurzburg, Versbacher Landstr. 5, D-8700 Wurzburg, FRG LANDRIGAN, PHILIPP J., Environmental Sciences Laboratory, Mount Sinai School of Medicine of The City of New York, 10 East 102nd Street, New York, NY 10029, U.S.A. LA VOlE, EDMOND J., Naylor Dana Institute for Disease Prevention, Ameri can Health Foundation, Valhalla, NY 10595, U.S.A. NEUMANN, HANS-GUNTER, Institut fUr Pharmakologie und Toxikologie, Universitat Wurzburg, Versbacher Landstr. 9, D-8700 Wurzburg, FRG ORLANDI, MARIO A., American Health Foundation, 320 East 43rd Street, New York, NY 10017, U.S.A. PREUSSMANN, RUDOLF, Institut fUr Toxikologie und Chemotherapie, Deut sches Krebsforschungszentrum, 1m Neuenheimer Feld 280, D-6900 Heidelberg, FRG PURCHASE, lAIN F. H., Central Toxicology Laboratory, Imperial Chemical Institutes PLC., Aldedey Park near Macclesfield, Chesire SKlO 4TJ, U.K. SCHWARZ, LESLIE, Institut fUr Toxikologie der Gesellschaft fur Strahlen und Umweltforschung, D-8042 Neuherberg, FRG SELIKOFF, IRVING J., Environmental Sciences Laboratory, Mount Sinai School of Medicine of The City University of New York, 10 East 102nd Street, New York, NY 10029, U.S.A.