Treatment factors rather than genetic variation determine metabolic syndrome in childhood cancer survivors

Background: Genetic variation that regulates insulin resistance, blood pressure and adiposity in the normal population might determine differential vulnerability for metabolic syndrome after treatment for childhood cancer. Objective: To evaluate the contribution of candidate single nucleotide polymorphisms (SNPs) relevant for metabolic syndrome in our single centre cohort of adult long-term childhood cancer survivors. Methods: In this retrospective study 532 survivors were analysed. Median age at diagnosis was 5.7 years (range 0.0-17.8 years), median follow-up time was 17.9 years (range 5.0-48.8) and median age at follow-up was 25.6 years (range 18.0-50.8). JAZF1 gene rs864745, THADA gene rs7578597, IRS1 gene rs2943641, TFAP2B gene rs987237, MSRA gene rs7826222, ATP2B1 gene rs2681472 and rs2681492 were genotyped. The association of genotypes with total cholesterol levels, blood pressure, body mass index, waist circumference and frequency of diabetes were assessed. Results: Metabolic syndrome was more frequent in cranially (23.3%, P = 0.002) and abdominally (23.4%, P = 0.009) irradiated survivors as compared with non-irradiated survivors (10.0%). Association of allelic variants in rs2681472 and rs2681492 with hypertension, rs987237 and rs7826222 with waist circumference and rs864745, rs7578597 and rs2943641 with diabetes were not significant. None of the SNPs was associated with the metabolic syndrome. Adjusting for age, sex, follow-up time, cranial irradiation and abdominal irradiation did not change these results. Conclusions: Treatment factors and not genetic variation determine hypertension, waist circumference, diabetes and metabolic syndrome in adult long-term survivors of childhood cancer.