Long-term genetic and reproductive effects of ionizing radiation and chemotherapeutic agents on cancer patients and their offspring.

The continuing search for a cure for cancer has lead to more aggressive therapies as new agents are developed with largely unknown late complications. Standard therapy for the majority of cancers today, following surgery, often consists of combinations of high doses of radiation and multi-drug therapy. Compared with exposures experienced by atomic bomb survivors, cancer survivors have been exposed to higher doses of partial body irradiation and combination chemotherapy over longer periods. Thus, cancer survivors provide a model system with which to evaluate the long-term effects on the human organism of high doses of agents known to damage DNA. Five-year survival after cancer diagnosis is now greater than 56%; more than 5 million Americans are considered cured of cancer. However, the late complications of cancer in long-term survivors has been poorly evaluated, especially in adults, and little is known of the most troubling possibility, that is, that the effects of cancer treatments could be passed on to the next generation. What little we know comes from studies of at most 5,000 survivors of childhood cancer, treated decades ago. So far, results are reassuring that with the means now available, we cannot detect clinical evidence of heritable damage. However, reproductive effects, including infertility, are common consequences of cancer therapy and may represent germ cell damage. We are just in the infancy of studies of germ cell mutagenesis in cancer survivors. The relatively small numbers of survivors, and the few types of exposures studied so far, provide only limited grounds for reassurance. More comprehensive, properly designed, studies of modern new agents are urgently need.