September 02, 2022
2 min read
Survivors of childhood cancer are at risk for experiencing a high burden of long-term chronic health conditions, including high rates of obesity in adulthood, in part related to specific cancer treatments.
Importantly, obesity in cancer survivors may compound risk for a number of health outcomes, including late cardiovascular disease.
“Survivors have a higher prevalence of obesity, but some of them also have received cardiotoxic cancer therapies, which places them at even higher risk for cardiovascular morbidity and mortality,” Yadav Sapkota, PhD, assistant member in the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, told Healio. “Among survivors with obesity who have also been exposed to cardiotoxic therapies, the risk for adverse outcomes actually becomes multiplicative. That is why we really need to understand who is at higher risk for obesity, so that we can suggest individualized treatments and prevention strategies.”
In a study published in Nature Medicine, Sapkota and colleagues evaluated the contribution of genetic risk scores in predicting obesity among childhood cancer survivors. Sapkota spoke with Healio about the study’s findings and implications.
Healio: How did you conduct this study?
Sapkota: Sex, age and other demographic characteristics are, to some extent, associated with risk for obesity. We know from studies in the general population that many genetic factors contribute to BMI. In terms of survivors, we also know that specific treatments can be predictive. So, we generated a risk prediction model for severe obesity, defined as BMI of 40 kg/m2 or greater, using survivor and treatment characteristics and lifestyle factors, as well as genetic factors. This model provides an estimated probability or likelihood of developing severe obesity. We then looked at the two largest cohorts of childhood cancer survivors in North America, the St. Jude Lifetime Study (SJLIFE) and Childhood Cancer Survivor Study (CCSS). We characterized obesity and developed the model using the SJLIFE cohort study, and we validated that model with the CCSS.
Healio: How did the model perform?
Sapkota: The model performed very well. Among 2,548 individuals from the SJLIFE cohort study who were 5-year survivors of childhood cancer, the genetic risk score was associated with 53-fold higher risk for severe obesity. Adding genetic risks scores to risk prediction models based on cancer treatment exposures and lifestyle factors yielded significantly improved model prediction, leading to the identification of 4.3 times more high-risk patients.
One obvious difference between the two cohorts is that the SJLIFE cohort utilizes height and weight values measured in clinic to calculate BMI, whereas the CCSS uses self-reported height and weight. BMI is often underestimated with self-reporting, as people generally tend to underreport their weight and overreport their height.
Healio: What interventions or preventive measures should be initiated for patients with a high BMI risk score?
Sapkota: To my knowledge, there are no studies evaluating prevention strategies for obesity based on genetic risk. However, in the literature there have been multiple studies in the general population that have shown a benefit of lifestyle or pharmacological interventions in reducing cardiovascular risk among individuals at higher genetic risk. So, it seems reasonable to evaluate similar interventions in those who are at high genetic risk for obesity.
Healio: What is next for your research in this area?
Sapkota: Our study demonstrates that genetics plays a very strong role in the development of severe obesity. Using this information to identify high-risk survivors may provide opportunities earlier in life for interventions to reduce risk. In translating these findings to the clinic, we will have to evaluate the feasibility and efficacy of intervention measures. We all know we need to follow a healthy lifestyle, but our goal is to evaluate whether using information about extremely high genetic risk for obesity will motivate these healthy behavioral practices in the growing population of childhood cancer survivors.
For more information:
Yadav Sapkota, PhD, can be reached at St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678; email: firstname.lastname@example.org.