CANCER: AN ENIGMA IN BIOLOGY AND SOCIETY CANCER AN ENIGMA IN BIOLOGY AND SOCIETY R. Nery, DSc, FRSC, qp CROOM HELM London & Sydney THE CHARLES PRESS, PUBLISHERS Philadelphia © 1986 R. Nery Softcover reprint of the hardcover 18t edition 1986 Croom Helm Ltd, Provident House, Burrell Row, Beckenham, Kent BR3 1A T Croom Helm Australia Pty Ltd, Suite 4, 6th Floor, 64-76 Kippax Street, Surry Hills, NSW 2010, Australia British Library Cataloguing in Publication Data Nery, R. Cancer: an enigma in biology and society. 1. Cancer I. Title 616.99'4 RC261 ISBN-13: 978-1-4684-8093-1 e-ISBN-13: 978-1-4684-8091-7 DOl: 10.1007/978-1-4684-8091-7 and The Charles Press, Publishers, Suit 14K, 1420 Locust Street, Philadelphia, Pennsylvania 19102 Library of Congress Catalog Card Number: 85-0728-52 ISBN-l3: 978-1-4684-8093-1 CONTENTS List of Tables Preface 1 Outline of the Cancer Enigma 1 2 Historical Perspectives: Concepts 32 3 Historical Perspectives: Practices 83 4 Hormones and Cancer 138 5 Heredity and Cancer: Comparative Aspects 177 6 Heredity and Cancer: Human Aspects 206 7 Chromosomes and Cancer: General Principles 235 8 Chromosomes and Cancer: Human Aspects 279 9 Interpretations: Facts, Fancies and the Future in Oncology 319 Bibliography 371 Index 431 TABLES 1.1 Proportional Occurrence among all New Cases of 23 Cancer and Cancer Deaths, by Sex and Site, in the United States in 1978 4.1 Some Landmarks in the History of Hormones and 142 Cancer 4.2 Some Hormone Preparations in Common Use 156 5.1 Differential Susceptibility of Common Laboratory 198 Strains of Inbred Mice and of Their Breast Tissues to Spontaneous Mammary Neoplasia 6.1 Some of the Polyposis and Related Syndromes 215 Associated with Heritable Colon Cancer 6.2 Some Cancer-associated Conditions Showing 216 Autosomal Dominant Inheritance 6.3 Some Cancer-associated Conditions Showing 218 Autosomal Recessive Inheritace 6.4 Some Cancer-associated Conditions Showing 219 Sex-linked Recessive Inheritance 6.5 Some Miscellaneous Cancer-associated Disorders 220 with Mixed or Unknown Modes of Inheritance, or with Unknown Heritability 7.1 The Gene Map of Human Chromosomes 1 and 17 240 7.2 Chromosomal Distribution in the Four 267 Near-haploid Human Leukemic Cell Lines Which Are Currently Known 7.3 Some Recent Examples of Chromosomal 270 Anomalies Occurring in Families 7.4 The Principal Chromosome-breakage Neoplasia- 272 predisposing Syndromes, All Autosomal Recessive, and Their Major Associated Neoplasms, Anomalies, and Sensitivities (with Related Features) 8.1 Various Non-Hodgkin Lymphomas Showing 286 Significant Morphological Similarities 8.2 Some Karyotypes Found in Banding Studies of 292 Pre leukemias and Acute Lymphocytic Leukemia 8.3 A Partial List of the Known Translocations 295 Involving Chromosome 1 in Some Lympho- and Myeloproliferative Disorders 8.4 Chromosomes and Their Anomalies Showing 298 Preferential Involvements in Various Human Neoplasms 9.1 Proportions of Human Cancer Incidence or 332 Mortality Attributed to Various Different Factors According to Three Independent Estimates 9.2 A Complete List of Chemicals or Industrial Processes 334 for Which There is Sufficient Evidence for Their Association with Risk of Human Cancers at Specific Body Sites 9.3 Some Epidemiologically Derived Risk Factors for 336 Various Human Cancers To my daughter PREFACE For obvious practical reasons the subject of oncology has in creasingly been becoming artificially subdivided, e.g. into epidemiology, experimental carcinogenesis, pathology, im munology, genetics, and even microbiology. Most extant tre atments of the subject are multi-authored, even when they deal with just one of these various subdivisions. Moreover, the corresponding specialists have seen the cancer problem as one within the purview of their own calling. In nature, however, the problem is a unity: its immunology, biochemistry, genetics, and cell biology, for example, are closely interdependent. Con sequently, its proper appraisal requires detailed examination of all of the major parts, but with the primary aim of a single-minded and hence unified survey of the whole. The present work is an offering in this direction. It is addressed specifically to all practising oncologists, whether clinical or ex perimental, and generally to all serious students of the growth of oncology and medicine from ancient to modern times. The author is indebted to his many colleagues at the Institute of Cancer Research and elsewhere for valuable discussions, to the Institute's library and other offices for their unstinting help, and to the Institute for financial support during the many long and arduous years of preparation of this work. 1 OUTLINE OF THE CANCER ENIGMA 1.1 Introduction : The General Scope of the Enigma In Greek mythology, Proteus, an ancient demi-god of the seas, was guardian of the seals (the animal variety) of Poseidon, that lord of the waters and earthquakes whom the Romans later called Neptune. Among his divinatory and other attributes, Proteus could readily assume anyone of countless forms, all of which were different but all intended for one specific purpose: to confound detection and questioning. So elusive was he said to have been that all who would learn his secrets had first to find and identify him and then to devise means for holding him fast. Only then could any meaningful dialogue with Proteus even begin. Not surprisingly, they usually failed, even in these preliminary efforts. In the light of these attributes, Proteus could well be regarded as the mythical father of cancer, but with due allowances made for the fact that the chip has far surpassed the block in variety, quality and extent of such protean arts and crafts. Thus, the disease occurs in many distinct or overlapping forms, actually or potentially in volving all known species of multicellular organisms and all of the latters' tissues, most likely from the very dawn of metazoan evolution. Not even plants, nor the insects with which they de veloped the most ancient, universal, and impressive of symbiotic relationships known to evolutionary biology, are free of the dis ease. Neither are adult nervous and muscular tissues of higher organisms, despite the fact that cancer cannot become evident in the absence of cell division which, normally, does not occur in such tissues. Moreover, in its various basic manifestations, cancer so closely emulates the similarities and differences which characterize normal tissues and normal developmental processes that it is, at least on current information, impossible to distinguish it un equivocally from normalcy on the basis of any known single feature. For present purposes, usage of the terms 'neoplasia', 'tumour' and 'cancer' is simply conventional. Accordingly, neoplasia (literally 'new growth') refers to all neoplasms or tumours. In- 1 2 Outline of the Cancer Enigma itially, tumours denoted swellings caused mainly by inflammation but they now only indicate those which are neoplastic, whether benign or malignant. Cancer refers to all malignant tumours, although it is rarely still distinguished from leukemia (literally 'white blood'). Perhaps the best of the available definitions of a neoplasm is that of Willis (1952), as 'an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change'. In a recent discussion of this definition, Robbins et al. (1984) added that the abnormal mass 'is purposeless, preys on the host, and is virtually autonomous'. However, even such definitions are, at best, approximations (Section 1.2.1). For instance, in vivo, tumour autonomy develops slowly and perhaps never completely; and a feature of the 'conditional' neoplasms such as those caused in the ears of rabbits by the dye Scarlet Red (ct. Chapter Three, Section 3.6.3.5) is their tendency to regress with disappearance of the inciting stimuli. It is for such reasons as outlined above that the fundamental problems posed by cancer have remained those centred around questions of specificity, e.g. in definition, diagnosis, and treat ment. In the entirety of their scope, nature, and implications to health and society, though not in any of their specifics, the prob lems set cancer apart from any other known disease, whether the latter is a frankly environmentally caused disease such as smallpox, or a disease such as xeroderma pigmentosum whose cause is thought to be a specific, heritable genetic defect. From ancient times, there have been multifarious intranational and international attempts, recently becoming increasingly inter disciplinary, concerted, and accelerated, at delineation of the etiology and the developmental course of cancer in man, other animals, and plants. In their outcome, these attempts have im plicated the same heritable, adaptive, and other factors by which, naturally, species evolve, individuals develop, and both diversify. These factors include a large compendium of inherited genes or genetic traits which may be defined with some accuracy or be simply surmised, be single or multiple, or be common ('normal') or rare ('abnormal'). Sharing similar features is an even larger compendium of implicated, non-heritable factors. Within this sec ond category are environmental factors, which may, additionally, be specific or non-specific, public or private, or static or changing;