Metabolic syndrome detection with biomarkers in childhood cancer survivors

Abstract

Purpose: Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (Met S). Risk stratification is difficult after abdominal radiation because waist circumferenc e underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonograp hy. Methods: The NCEP-ATPIII MetS-components, 14 additional serum biomarker s and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment eff ects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations. Results: After 27.5 years of follow-up, MetS occurred more often in sur vivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with seve ral biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was a ssociated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value. Conclusions: Long-term childhood nephro- and neuroblastoma survivors freque ntly develop MetS. Additional assessment of biomarkers identified in PCA – adiponectin, LDL, apoB, and uric acid – may be used especially in abdominally irr adiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasono graphy was not of added value.

Keywords

• childhood cancer survivor
• metabolic syndrome
• nephroblastoma
• neuroblastoma
• principal component analysis
• biomarker