Influence of treatment, genetic predisposition, and lifestyle on cardiovascular risk factors among cancer survivors

Background As traditional cardiovascular risk factors increase cardiovascular risk with a near-multiplicative effect among childhood cancer survivors, our purpose was to evaluate the combined contributions of population-based polygenic risk scores and lifestyle behaviors to cardiovascular risk factors to identify targets for surveillance and risk prevention. Methods Participants included 2610 European ancestry childhood cancer survivors (mean [SD] age = 34.6 [9.5] years). Using phenotype-specific, population-based polygenic risk scores for low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides, fasting glucose, hemoglobin A1c, systolic blood pressure (BP) and diastolic BP, childhood cancer survivors were classified with low (lowest quintile), intermediate (middle 3 quintiles), or high genetic risk (highest quintile). Lifestyle (good, intermediate, poor) was based on 4 factors (smoking, physical activity, diet quality, obesity). Multiple linear regression was used to assess associations between lifestyle and genetic risk with each cardiovascular risk factor, adjusting for cancer therapies and medications. Results Worsening cardiovascular risk factor profiles were associated with poorer lifestyle (ie, decreasing number of positive health habits) and increasing genetic risk. For example, poor lifestyle and high genetic risk were associated with a mean (SE) of 5.4 (1.0) and 5.0 (1.1) mmHg increase in systolic BP compared with good lifestyle and low genetic risk, respectively, and 3.4 (0.7) and 4.4 (0.7) mmHg increase in diastolic BP. Among childhood cancer survivors with high genetic risk, mean (SE) diastolic BP (mean = −4.6 [2.2] mmHg, P = .034) and fasting glucose (mean = −5.0 [2.1] mg/dL, P < .001) were lower among childhood cancer survivors with good vs poor lifestyle, while mean high-density lipoprotein was higher (mean = 12.9 [1.9] mg/dL, P < .001). Conclusion Among childhood cancer survivors, lifestyle is associated with increased risk of cardiovascular risk factors independent of genetic risk and treatment, highlighting the importance of developing interventions targeting lifestyle in this population.