Research demonstrates that adult survivors of childhood cancers are at an augmented risk of numerous chronic health conditions. Of particular concern are conditions that can affect the heart due to toxicities associated with certain cancer therapies. Adult survivors of childhood cancer also have elevated rates of obesity, which is a major risk factor for cardiac disease.
In a recent press release from St. Jude Children’s Research Hospital, researchers pooled genetic and clinical risk factors to establish a method to predict which childhood cancer patients are most likely to develop severe or “morbid” obesity as adults. The tool will give physicians and survivors the information to aid them in encouraging positive lifestyle changes. Their findings were also published in a recent publication in Nature Medicine.
Utilizing the tool, researchers calculated that survivors with the greatest genetic risk score were 53 times at a greater risk of obesity compared with survivors with the lowest genetic risk score. The risk of obesity was independent of other general risk factors.
The researchers indicated that the St. Jude method provides an opportunity for targeted interventions for children and their families to adopt healthy lifestyles early in life to prevent obesity in adulthood; this research is one of the first studies to demonstrate the influence of genetics and treatment-related risk factors to augmented risk of developing obesity and related traits that survivors experience compared with the general population.
In the studty, researchers employed their genetic risk models to more than 4,000 St. Jude childhood cancer survivors enrolled in the St. Jude Lifetime Cohort Study (St. Jude LIFE). Participants have had whole genome sequencing of their germline (inherited) DNA. St. Jude LIFE participants then return to St. Jude throughout their adult lives for regular health screenings.
The researchers examined how their tool performed in the survivor health data, predicting adult obesity in St. Jude LIFE childhood cancer survivors of European ancestry. The genetic risk score is an aggregate score derived from approximately 2.1 million common genetic variants correlated with BMI established in individuals of European ancestry in the general population.
When researchers applied the same method to a different cohort of adult survivors of childhood cancer, they discovered a slightly weaker signal, but the score still predicted severe obesity. The Childhood Cancer Survivor Study (CCSS) provided the second cohort of 6,064 survivors. CCSS is a retrospective analysis of cancer survivors at least 5 years posttherapy treated at one of 31 institutions in the U.S. and Canada.
The researchers also noted that while their findings hold remarkable value for childhood cancer survivors of European ancestry, the genetic risk score was not predictive of obesity in individuals of African ancestry in either cohort. The researchers addressed this issue by creating a different genetic risk score tailored for individuals of African ancestry.
The authors concluded, “We developed a prediction model for severe obesity and validated the model in an independent cohort of survivors. Although clinical, treatment and lifestyle risk factors contribute to the risk of severe obesity in survivors, inherited genetic factors contribute appreciably to the risk. Genetic testing, along with assessment of clinical risk factors, could be used to identify survivors at high risk for severe obesity who may benefit from aggressive primary interventions as early as at the time of cancer diagnosis as well as secondary interventions.”
Lead and co-corresponding author Yadav Sapkota, PhD, at the St. Jude Department of Epidemiology and Cancer Control, stated, “It is important for childhood cancer survivors to know if they are at risk for developing various chronic conditions. We have developed a prediction model that can help healthcare providers identify which survivors are likely to develop severe obesity.”
Co-corresponding author Yutaka Yasui, PhD, at the St. Jude Department of Epidemiology and Cancer Control, noted, “This is a really important advance for the care of survivors. We can identify the highest risk survivors with this method—a genetic method. We can know which childhood cancer patients are high risk for severe or other obesity early on in life, so we can give personalized advice to them.”
“In the future as this type of genetic testing becomes more clinically available, this knowledge will provide clinicians with the opportunity to intensify efforts to promote healthy weight maintenance in survivors at high risk for severe obesity. Good nutrition and regular physical activity are important for all cancer patients but are particularly important for those with genetic and treatment risks associated with obesity,” stated Melissa Hudson, MD, coauthor and coleader of the St. Jude Cancer Control and Survivorship Program.
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