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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."
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