Cancer And Heredity
( Originally Published Early 1960's )
The question, "Is it heredity or environment?" is now seldom heard, because it is really not very meaningful. The effects of any environmental stimulus on an organism are modified by the inherited traits of the organism, and the inherited traits and capabilities of an organism can be modified by the external or internal environment.
Cancer research began in earnest at the turn of this century, and its first materials were the breast cancers in small laboratory rodents. It was noted that cancers occurred more frequently in certain families of such animals, and it was postulated that such familial aggregation involved genetic factors. For the resolution of these factors, genetically defined animals were necessary, and these were developed by brother-to-sister selective breeding.
A long series of investigations by geneticists using inbred strains led to the conclusion that cancer was not a single genetic characteristic, and that different mosaics of genetic factors were involved in the susceptibility to different cancers. Strains of mice that developed lung tumors, for example, could be relatively resistant to liver tumors. In general, if a high cancer strain was crossed with a low cancer strain, the hybrids showed an intermediate susceptibilty to cancer. There were some exceptions, but in general the frequency of cancer in the hybrid cannot be predicted by knowing the frequency of the occurrence in the parent strains. Walter Heston of the National Cancer Institute, in his studies of lung tumors in mice, showed association of susceptibility to a number of identified genes. The important studies on breast cancer in mice revealed the presence of an extra chromosomal factor that led to the discovery of the Bittner virus. But for the occurrence of breast cancers in mice, the genetic background modifies susceptibility to the virus and remains of importance. In some strains of mice that develop but few breast cancers, the introduction of the Bittner virus converts the strain to a high cancer line in subsequent generations. In others, the incidence of breast cancer drops sharply after a few generations, as the virus disappears. Here the genetic constitution of the animals overcomes the carcinogenic virus and its manifestations.
The mosaic of hereditary factors thus participates in every step of the cancer process : at the reaction to the carcinogenic compound or virus, to the tissue susceptibility to the neoplastic transformation, and to the subsequent growth and metastasis of the cancer. The immune mechanisms that are involved in the acceptance or rejection of tissues are also dependent upon the genetic constitution of the organism.
In animal species whose breeding patterns man wishes to manipulate, it is possible to segregate and develop lines of high frequency of specific cancers, as was done in mice. It is also possible to reduce cancer occurrence by selective breeding techniques. For example, the problem of cancer of the skin around the eyes of white faced Hereford cattle that are exposed to high levels of solar radiation could be reduced or eliminated by introducing more protective skin color. As in all purposeful genetic choices, however, such a change may be associated with many other unpredicted and even less desirable new characteristics. As another example, the occurrence of liver cancer in trout is most evident in the rainbow species, and much less so in other trout varieties. It is predictable that this neoplasm also could be reduced by breeding techniques, although the identification and the elimination of the carcinogenic factors in the diet appears to be a more desirable and more informative attack on the problem.
In human populations, most of the common forms of cancer do not show obvious familial aggregations. Special studies, however, do reveal relatively minor degrees of such aggregation in cancer of the breast, rectum and lung. Familial aggregation of a characteristic does not in itself indicate a hereditary factor, since families also share common environmental situations. The hybrid nature of the human species makes exact genetic studies difficult. Some clarification of the relative roles of heredity and environment is afforded through registries of identical and fraternal twins.
There are some cancers and precancerous conditions in man that are primarily determined by the heredity of the individual. Retinoblastoma, a tragic cause of blindness and death in children, is inherited as a dominant trait, and the presence of this trait has been suggested as a valid reason for eugenic sterilization of the parent so afflicted. An abnormal sensitivity of the skin to ultraviolet radiation, called xeroderma pigmentosum, almost inevitably develops into cancer, and is a hereditary disease. So is the familial multiple polyposis of the colon, which develops into cancer during the second and third decade of life.
It should be pointed out that the occurrence of skin cancer in man has a strong hereditary factor, in that the characteristic of dark skin protects the individual against the carcinogenic effects of ultraviolet radiation.
As a practical point of advice to relatives of patients with cancer, we now should avoid a blanket statement that cancer is not inherited. For most specific cancers, it is better to say that the risk of developing such a cancer by the relatives is no greater than that of the general population. But the daughters and sisters of women with breast cancer, and the children of patients with rectal cancer should be informed of their increased risk, genetic or otherwise, which makes desirable closer medical surveillance.