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Genetic epidemiology of familial aggregation of cancer

, : Genetic epidemiology of familial aggregation of cancer. Advances in Cancer Research 47: 1-36

Literature pertaining to genetic epidemiological studies of familial cancer has been reviewed from a historical perspective. Although interest in the question of heritability of cancer was extant at least as early as the beginning of the nineteenth century, early investigators were unable to produce consistent and meaningful evidence pertaining to the issue because of unsystematic methods of data collection and inadequate methods of data analysis. During the early twentieth century, developments in the fields of genetics, statistics, and epidemiology provided concepts and methods that permitted investigators to recognize important deficiencies in past studies, and to design others in which the critical comparisons could be made between patient groups and control groups. Registries of cancer incidence in large populations became available in several countries in the middle twentieth century, providing a standard "control group" for comparison. Large surveys of site-specific cancer experience in families, rigorously designed and analyzed, found for most kinds of cancers a two- to threefold increased risk for close relatives of propositi. These studies also reemphasized the great difficulty in obtaining even minimally complete family health history information, and the importance of verifying all reported cases with medical or vital records. Although clinical and laboratory investigation will be necessary to understand the mechanisms by which human genes may predispose to cancer, epidemiological approaches can estimate the extent to which genetic etiological factors may be present in a population, whether a general population or one defined by other factors under investigation. Population-based studies are already of practical significance to the clinical geneticist in the estimation of risk of eventual cancer development in unaffected family members, and can be expected to continue to identify specific groups and characteristics associated with genetic cancer predisposition. Finally, segregation and linkage analysis and their present applications to family studies of cancer were reviewed. As a result of the increasing number of DNA polymorphisms that are becoming available due to developments in molecular biology, the human gene map can be expected to be well defined in the near future, and investigation of families using segregation and linkage analysis will then be instrumental in defining the role of heredity in the development of cancer in human populations.


PMID: 3535425

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