Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors

Abstract

Abstract Background In childhood (CCS) and testicular cancer (TCS) survivors, low-grade inflammation may represent a link between testosterone deficiency (hypogonadism) and risk of metabolic syndrome. We aimed to study levels of inflammatory markers in CCS and TCS and the association with hypogonadism and future cardio-metabolic risk factors. Methods Serum levels of inflammatory markers and testosterone were analyzed in CCS (n = 90), and TCS (n = 64, median time from diagnosis: 20 and 2.0 years, respectively), and in controls (n = 44). Differences in levels between patients and controls were calculated using univariate analysis of variance. T-test and logistic regression were applied to compare levels of cardio-metabolic risk factors and odds ratio (OR) of hypogonadism and metabolic syndrome in low and high inflammatory marker groups after 4–12 years of follow up. Adjustment for age, smoking, and active cancer was made. Results TCS and CCS, as compared to controls, had 1.44 (95%CI 1.06–1.96) and 1.25 (95 CI 1.02–1.53) times higher levels of IL-8, respectively. High IL-6 levels were associated with hypogonadism at baseline (OR 2.83, 95%CI 1.25–6.43) and the association was stronger for high IL-6 combined with low IL-10 levels (OR 3.10, 95%CI 1.37–7.01). High IL-6 levels were also associated with higher BMI, waist circumference, insulin, and HbA1c at follow up. High TNF-α was associated with higher diastolic blood pressure. No individual inflammatory marker was significantly associated with risk of metabolic syndrome at follow up. High IL-6 combined with low IL-10 levels were associated with risk of metabolic syndrome (OR 3.83, 95%CI 1.07–13.75), however not statistically significantly after adjustment. Conclusion TCS and CCS present with low-grade inflammation. High IL-6 levels were associated with hypogonadism and cardio-metabolic risk factors. Low IL-10 levels might reinforce the IL-6 mediated risk of developing metabolic syndrome.