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 (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography.

Methods: The NCEP-ATPIII MetS-components, 14 additional serum biomarkers 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 effects. 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 survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several 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 associated 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 frequently develop MetS. Additional assessment of biomarkers identified in PCA - adiponectin, LDL, apoB, and uric acid - may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.

Keywords: biomarker; childhood cancer survivor; metabolic syndrome; nephroblastoma; neuroblastoma; principal component analysis.

Figure 1

Biplots of PCA (principal components 1 and 2) of serum biomarkers, with the effect of abdominal radiotherapy (A) and nephrectomy (B). Score on PC1 and PC2 is a Z-score, based on loadings and Z-scores of biomarkers. ApoA1, apolipoprotein-A1; ApoB, apolipoprotein-B; FFA, free fatty acids; HDL, high density lipoprotein cholesterol; HOMA, homeostasis model assessment; LDL, low density lipoprotein cholesterol; Lpa, lipoprotein(a).