Genetic and family studies

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Abstract

It is important not only to know what causes cancer, but also who is most or least susceptible, and why. Family clusters of cancer may occur for genetic reasons. The tumors may be of the same type, of dissimilar types or they may be associated with nongenetic diseases. In one family, for example, seven members developed renal cell carcinoma. The study of unaffected members in the line of descent revealed three more cases. Examination of the chromosomes in lymphocytes and skin fibroblasts revealed that the affected members had a translocation from chromosome 3 to chromosome 8. The patients had no signs of other disease, such as congenital malformations. Examination of relatives too young to have developed renal cell carcinoma revealed that several had the 3/8 translocation and were therefore at high risk of renal cell carcinoma. By frequent examination, the tumor can be detected early, and life‐saving treatment can be promptly administered. Purtilo and his associates have described an X‐linked susceptibility to diseases of the B lymphocytes, including lymphoproliferative disorders and fatal infectious mononucleosis. In these families multiple male members develop these diseases, which represent an interaction between host susceptibility and an Epstein‐Barr virus (EBV). Production of a vaccine against EBV infection could be tested for its effectiveness in such families. Interactions are also known between host susceptibility and physical agents. The inability of patients with xeroderma pigmentosum to heal DNA damage caused by exposure to sunlight is a case in point. In ataxiatelangiectasia, the patients are unable to heal DNA damage due to gamma radiation exposure. The DNA damage is not the same in the two disorders. Protecting patients with XP from sunlight can prevent or at least delay the occurrence of frequently fatal skin cancer. Protecting patients with AT from therapeutic radiation (for the lymphomas to which they are prone), can prevent acute radiation reaction. From such rarities, we have learned a great deal about cancer biology. This new information about host susceptibility and carcinogenic mechanisms may lead to new means for prevention or early detection of cancer.