Adverse reproductive effects of treatment for cancer in childhood and adolescence

Abstract

Modern treatments for cancer include high doses of ionising radiation and combinations of highdose systemic chemotherapy. Although these curative therapies have the potential to produce germ-cell mutations leading to genetic disease in the next generation, there is still little understanding of the genetic consequences of such treatments. To date, no environmental exposure has been proven to cause new heritable disease in human beings [1]. Childhood cancer is a success story of modern medicine in which effective treatments have been identified for previously untreatable disease. With the lifesaving advances in treatment introduced after 1970, using combinations of multiagent chemotherapy, surgery and radiotherapy, the overall 5-year survival after cancer has reached 81% for children and 87% for adolescents and young adults [2]. The continuing rise in survival rates for young cancer patients, and the ability for survivors to have children of their own, have highlighted the importance of evaluating the impact of cancer therapy on fertility, pregnancy and health of the growing number of children of cancer survivors. Cancer survivors offer one of the largest groups of people exposed to high doses of potent mutagens before reproductive age [3], and the timing and dose of their exposure to radiotherapy and mutagenic chemotherapy are accurately documented in their medical records [4]. Their curative radiation and chemotherapy treatments can result in non-sterilising gonadal exposures that offer a special opportunity for studying possible genetic changes that are inherited by their children. Preconception cancer treatment in cancer survivors might cause trans-generational germ cell mutations and, if so, these mutations might lead to adverse pregnancy outcomes or a clinically recognisable disease in the offspring. Some of these outcomes, however, may have been familial rather than the result of a new mutation, and others might be the result of radiation-induced somatic mutations. This paper gives an overview of the evidence for trans-generational effects including untoward outcomes of pregnancies such as spontaneous abortions and stillbirths, and health problems in the offspring, the main emphasis being laid on cancer in the next generation.