A Genetic Study of Induced Lung-Tumours in Mice

THOUGH there is now abundant proof of the importance of genetic factors in the causation of many forms of cancer (Heston, 1959), the precise mode of inheritance has proved difficult to establish, even in mice, on which many genetic studies have been made. The development of inbred strains of mice showed at once that there are genetically determined differences of susceptibility to various forms of cancer, both spontaneous and induced, since inbred strains kept under the same conditions were found to differ from each other. Genetic studies of crosses between differing strains, however, did not reveal the Mendelian ratios in the segregating F2 and backcross generations that were to be expected if the inheritance was simple. The strains were thus shown to differ by more than one or even a few genes affecting susceptibility, and the inheritance was proved to be multifactorial, or quantitative (Heston, 1942a, b). This, unfortunately, makes genetic studies much more difficult, both technically and conceptually, and little progress has been made in advancing the study of cancer into the field of quantitative genetics. One technical difficulty is simply the need to study much larger numbers of individuals than are required for Mendelian analysis, but perhaps a greater one arises from the fact that it is no longer sufficient to distinguish between susceptible and non-susceptible individuals, because there are degrees of susceptibility. It is therefore necessary to find some means of measuring the degree of susceptibility. The conceptual difficulties arise because the genetic questions to be asked are of a different sort and are largely unfamiliar to those who are not specialists in this branch of genetics. Moreover, the well-known methods of genetic analysis by the study of ratios are no longer appropriate and other methods, involving more complicated statistical treatment of the data, are required. This paper describes an analysis of urethane-induced pulmonary adenomas in mice by methods appropriate to multifactorial inheritance. A general account of these methods and the underlying principles may be found in Falconer (1960a). A preliminary report of part of the work was given by Falconer and Bloom (1961). Pulmonary tumours were chosen for study because the multiple tumour-nodules provide a means of measuring quantitatively the degree of susceptibility of individual mice, the number of tumours detectable at a fixed age being taken as a measure of susceptibility. It will be shown later that the number of tumours does not provide an …