Since the success in chemical induction of cancer in rabbit's ear skin by K. Yamagiwa in 1915, oncologists of the world have come to believe that they can only solve their problems by means of animal experimen tation. The importance of environmental factors became moreevident in 1935 when T. Yoshida and T. Sasaki introduced azodye hepatocarcino genesis in rats. In the domain of the gastrointestinal tract, T. Sugimura has more recently accumulated enough evidence to indicate that locally active chemical mutagens are carcinogenic. In contrast, principal approaches to colorectal tumors have been quite different: emphasis has been placed on gene identification. Long before cancer of the large bowel was recognized, importance of the roles of adenomatosis coli and its familial occurrence attracted the attention of epidemiologists and geneticists. Morphological characteri zation and analysis of hereditary trends of human material have already bad a long history, and recently detailed analysis of genetic material has become feasible in the wake of rapid development in our knowledge of the oncoviruses, oncogenes, suppressor genes, chromosomal and DNA mapping, molecular mutation and so on. lt is true that in colorectal pathology, and in no other field, these areas of research have been explored more extensively and decisively. The identification of previ ously ill-defined lesions such as precancers and benign neoplasms have been improved because sequential changes can be observed in multiple samples spread over a wide area and followed up in due course.

The writing of this monograph was stimulated on the one hand by experience gained in the study of "cancer families," and on the other, by the frequent perplexed and bewildered comments made by numerous physicians who have expressed amaze ment that we could think that "cancer is hereditary." In reviewing the world literature it became immediately apparent that no compendium on the subject of cancer genetics was available to the physician or research scientist. Therefore this monograph has been written for the following reasons: 1) To illuminate the problem for those who may have missed or ignored the evidence supporting a genetic etiology for certain malignant neoplasms; 2) to supply useful information to all practicing physicians regarding genetic risks to their patients; and 3) to provide new thoughts on the subject for use by cancer investigators. Finally, our paramount hope is that information gleaned through the reading of this monograph may contribute to the early dia gnosis of cancer in members of high risk "cancer families.""

The discipline of genetic epidemiology pertains to the vertical transmission of the susceptibility (predisposition) to a complex disease in a structured population. This statement meets halfway 1 the broad definitiongiven by N. E. Morton and S. c. Chung in 1978 2 and the concise one given by M. -C. King et al. in 1984. 1t pinpoints the fundamental genetic hypothesis, namely, the existence of an inherited condition that predisposes an individual to a specific disease, and the corresponding subject ofinvestigation, the family. Thus, the genetic epidemiological situation consists of three basic elements: (l) the genealogical structure, (2) the mode of inherit ance (i. e., the "genetic model") for the trait of interest, and (3) the observable phenotypes of susceptibility. It is clear that genetic epidemiology is a research field posi tioned at the intersection of molecular genetics, population gen etics, and clinical genetics. Perhaps the genealogical tree should be its central element: it evidences something forgotten in mole cular genetics, namely the relationships, and associations with probabilistic and statistical concepts from population genetics. It offers a structure and a "history" for those clinicians studying familial diseases who are searching for genetic determinants of susceptibility. The genetic epidemiologist begins his analysis with a point on this genealogical tree, namely the proband, and attempts to carry out (nonrandom) "ascertainment sampling" by using a strategy that depends on the form and dimension (extended pedigrees versus nuclear families) of the tree."