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• A marked susceptibility to carcinoma exists in the case of certain family generations and family groups. • This susceptibility is frequently associated with a marked susceptibility to tuberculosis, and also with reduced fertility. The striking association of tuberculosis with cancer in certain families has also been noted by Kuthy and Williams. • The multiple occurrence of carcinoma in a family generation practically always means its occurrence in a preceding generation. • The family tendency is usually more marked when carcinoma occurs in both maternal and paternal lines. • Family susceptibility to carcinoma is shown particularly in the case of carcinomas of the mouth, lip, breast, stomach, intestines, and uterus. • In a family showing the occurrence of carcinoma in several generations, there is a decided tendency for the neoplasm to develop at an earlier age in the members of the youngest generations. In this case, the neoplasm often shows an increased malignancy. • Because of the difficulty of obtaining complete family records, the laws of inheritance of carcinoma susceptibility cannot be determined accurately, and it is highly desirable that investigations of large family records be made relative to the occurrence of carcinoma susceptibility. In Levin's study of cancerous fraternities in connection with the whole family history, the percentage of cancerous members in each cancerous fraternity corresponds very closely to the Mendelian percentage of members with recessive unit-characters in a hybrid generation. The same conclusion might be drawn from my cases in certain instances, but it does not seem to me that the data are sufficient for such conclusions. Levin himself does not consider this conclusion as final. He also concludes that resistance to cancer is a dominant character whose absence creates a susceptibility to cancer. While some of my cases show a family history suggesting this, others would indicate a progressive degenerative inheritance—the running-out of a family line through the gradual development of an inferior stock, particularly as far as resistance to tuberculosis and cancer is concerned. Levin, as well as Williams, noted the family tendency to specific localization of the cancer, particularly of the uterus in the women, and of the gastrointestinal tract in the men. This is well shown in my family histories and in some of the cancerous fraternities. Levin concludes that the most important result of his investigation is the fact that it shows the presence of an inherited resistance to cancer growth. I would put it in just the opposite way and say that my observations are important in that they show in certain families an inherited susceptibility to cancer. If the majority of the human race do not show this susceptibility, resistance to cancer is a normal trait of the species. An increased susceptibility becomes, therefore, the abnormal character of importance, and our investigations should be carried out along the line of attempting to determine just what lies back of this susceptibility.
Heredity with Reference to Carcinoma As Shown By the Study of the Cases Examined in the Pathological Laboratory Of the University of Michigan, 1895-1913
Aldred Scott Warthin M.D.
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