Chronic health conditions in childhood cancer survivors: is it all treatment-related--or do genetics play a role?
BACKGROUND
High-intensity, risk-based therapeutic strategies for childhood cancer have resulted in long-term survival rates that now approach 80%. However, the growing population of survivors is at a substantial risk for treatment-related complications that can significantly impact quantity and quality of survival. It is increasingly recognized that many of these complications result from complex interactions between therapeutic exposures and genetic susceptibility.


OBJECTIVE
This review is designed to increase general clinician awareness of the ongoing efforts by investigators to understand the interactions between therapeutic exposures and genetic susceptibility to therapy-related complications.


RESULTS
Most studies have relied on a biologically plausible candidate gene approach to evaluate genetic susceptibility. This has resulted in the identification of unique genetic polymorphisms that could alter metabolic pathways of therapeutic agents associated with specific adverse events. We highlight some of these findings and discuss their implications for future prevention strategies, as well as their role in elucidating the pathophysiology of these complex diseases.


CONCLUSIONS
Research exploring the role of genetic susceptibility in the development of therapy-related adverse outcomes is still in its infancy. There is a need for continued efforts to study these outcomes in the context of complex gene-gene and gene-environment interactions unique to cancer survivors. A better understanding of the pathogenesis of these outcomes will help develop effective targeted prevention strategies.
Department of Population Sciences, City of Hope National Medical Center, Duarte, CA, USA.
Saro H
SH
Armenian
Smita
S
Bhatia
D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D006304:Health Status; D006333:Heart Failure / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D000970:Antineoplastic Agents