Effects of cancer treatment on individual and generational genetics

THE DEVELOPMENT of antineoplastic analysis of the incidence of second malignancies in untreated patients. As the oncogenic potential of radiotherapy and/or chemotherapy is incompletely known, more recent analyses only permit conclusions as to an increased incidence when the second neoplasm is identified concurrent with or shortly after the index neoplasm. The studies of Berg et al.‘T2 used a New York State control population to examine two questions: (1) Was the incidence of other primary cancers increased following leukemia or lymphoma? (2) Did tumors of the nasal cavity, paranasal sinuses, or nasopharynx predispose patients to other neoplasms? They found that the incidence of second neoplasms was increased ninefold, fourfold, and 25fold following myeloid leukemia, lymphatic leukemia, and malignant lymphoma, respectively. The predominant site involved was the skin, and no single common cause for this increase was identified. Of patients with primary cancer in the nasal cavity, sinuses, or nasopharynx, second malignancies occurred more frequently than expected and were seen in the skin 20% of the time and in the upper digestive system 73% of the time. In a study of similar design, Schoenberg et a1.3 found that women with breast cancer had a 1.5fold increased incidence of a second neoplasm of the colon, ovary, or uterus. Further, uterine or cervical primaries were associated with a similar increase in rectal cancer. Moertel and Hagedorn4 reviewed a large group of patients with chronic leukemia, acute leukemia, and reticulum cell sarcoma seen at the Mayo Clinic between 1944 and 1953 and found a variety of solid tumors presenting concurrent with the primary malignancy. Hyman5 has extended these observations in chronic lymphocytic 1 chemotherapy has made major advances since the introduction of antitumor agents into clinical use in the 1940s. Therapeutic programs have grown progressively more complex employing several different kinds of drugs and frequently combining radiotherapy and chemotherapy. These therapy programs have produced impressive results in the therapy of a variety of neoplasms, particularly acute lymphocytic leukemia (ALL), Hodgkin’s disease and the non-Hodgkin’s lymphomas, testicular tumors, trophoblastic tumors in women, and Wilms’ tumor and rhabdomyosarcoma in children. With prolonged survivals and “cures” being affected, patients are now alive long enough for the potential late toxicity of their original therapy to appear. Thus, many patients are now at late risk for the development of second tumors. Moreover, as many therapies are potentially teratogenic, those patients that remain capable of reproducing may have an altered gene pool in their gametes. Ethical questions cannot help but arise as to the long-term benefits and potential hazards of such treatment and investigators must constantly monitor clinical trials to determine risk-benefit ratios. Whereas the hazards will be discussed in detail, their ethical implications will not be addressed in this article. Rather, we will confine ourselves to assessing the risks of anticancer therapy to both the individual and to subsequent generations.