Exploring germline genetics and treatment history to evaluate risk of late treatment effects in childhood cancer survivors.
Pediatric cancer treatments can lead to a variety of health problems for survivors once they reach adulthood. Determining a survivor’s risk for a particular late effect of cancer treatment will allow tailored screening and intervention to offset these effects. My research uses statistical/machine learning combined with biological/clinical reasoning to explore heritable genetics—DNA passed from parent to child—and therapeutic history to predict individual survivors’ personalized risk for different types of late effects from pediatric cancer treatment. The aim of this work is to improve survivors’ long-term outcomes and quality of life.
During the 1960s, only about 30% of children diagnosed with cancer had a five-year survival rate. Today, pediatric cancer survivorship in the United States has risen to approximately 85%. Yet, despite the increasing success for five-year survival, survivors are likely to develop a variety of late effects from therapy they received. These late effects may include secondary cancers, cardiovascular problems, respiratory issues, endocrine/fertility issues, and neurocognitive challenges, among others. Within the Department of Epidemiology and Cancer Control, our research aims to identify those at high risk for particular late effects, screen them with proper methods and frequencies, and intervene with specifically targeted interventions as early as possible to improve outcomes. We accomplish our work through extensive interdisciplinary collaboration with a myriad of scientists in the Cancer Control and Survivorship Program.
Our research, conducted through the Childhood Cancer Survivor Study (CCSS) and the St. Jude LIFE cohort, focuses on the genetic components underlying the late effects of cancer treatment. While cancer treatments may largely determine the risk for late effects, those risks are modified by an individuals’ germline genetics and inherited susceptibility to radiation sensitivity and chemotherapy toxicity. We aim to predict these risks statistically, with a focus on the combined impact germline genetics and therapies have on the risk for developing late chronic conditions associated with pediatric cancer treatment.
We also engage in fundamental methodological research to analyze germline genetic data in relation to disease risk, focusing on the joint influence of multiple loci. For example, while breast cancer is a widely studied phenotype with vast amounts of available data, the amount of risk attributable to germline DNA—known as ‘heritability’— remains only partially explained. Through this methodological study, we learn how germline genetics contributes to breast cancer risk, and we become better positioned to accurately determine survivor’s risk for the disease and other late effects.
As our research contributes to a growing body of knowledge about the role of germline genetics in childhood cancer late effects, we will be able to develop effective interventions that help offset late effects and chronic conditions that arise from therapeutic treatment.
Dr. Yutaka Yasui has dedicated over 25 years to childhood cancer survivorship research as a methodologist. His methodological research has focused on biologically/clinically informed analytic strategies for data in large-scale molecular/clinical epidemiological studies. Yasui, originally from Kyoto, Japan, received his PhD in Biostatistics from Johns Hopkins University in 1994, and his work has been published in over 450 peer-reviewed publications with more than 50,000 citations. Beyond his research, he dedicates himself to education efforts through the training of graduate students and postdoctoral fellows and by teaching biostatistics and (genetic) epidemiology at various levels of academia.
Yutaka Yasui, PhD
Member, Epidemiology and Cancer Control
Department of Epidemiology and Cancer Control
St. Jude Children's Research Hospital