Allogeneic transplantation and the risk for transmission of genetic disease: the heritable cancer disorders.
With the development of new approaches to transplantation therapy, such as those building upon the potential found in stem cells, it is vital to pursue a clear understanding of transplantation risks. Allogeneic transplantation presents risk for the transmission of disease of various types, including genetic disease. Predisposition to develop cancer is a feature of numerous genetic disorders, and it may be transmissible by transplantation. Some genetic disorders predisposing to cancer are remarkably common, either worldwide or in specific populations, and they could pose significant risk. Hence, to reduce risk to recipients, there is reason to exclude from donation those potential donors (including embryos) harboring certain germ-line mutations. However, the frequent absence of readily identifiable features might confound the effort to exclude those who harbor mutation. Thus, it is also important to consider the magnitude of risk that they represent. For some disorders, life-threatening cancer is highly likely to develop in those individuals born with germ-line mutation, but whether recipients would face the same risk from transplanted mutation is not always evident. Given the diversity of pathways that lead to cancer, there may be diverse factors that impact the likelihood for cancer to develop in the recipient, with some factors decreasing and others increasing the risk. One factor of special concern is the possibility that manipulation of donor cells, prior to transplantation, might introduce additional genetic or epigenetic abnormality, thereby increasing the risk.
McMilin
Kenneth D
KD
Alabama and Central Gulf Coast Region, American Red Cross Blood Services, Birmingham, AL 35205, USA. mcmilink@usa.redcross.org
Dasgupta
Susmita
S
D018450:Disease Progression; D030342:Genetic Diseases, Inborn; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D019683:Penetrance; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects*