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

BMC Cancer. 2022 Feb 9;22(1):157. doi: 10.1186/s12885-022-09253-5.

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.

Keywords: Cancer survivors; Hypogonadism; IL-10; IL-6; IL-8; Inflammation; Metabolic syndrome.

MeSH terms

  • Adolescent
  • Adult
  • Cancer Survivors / statistics & numerical data*
  • Cardiometabolic Risk Factors
  • Follow-Up Studies
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / etiology*
  • Inflammation
  • Inflammation Mediators / blood*
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Logistic Models
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / etiology*
  • Middle Aged
  • Odds Ratio
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / complications
  • Testosterone / blood*
  • Young Adult

Substances

  • IL10 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-10
  • Testosterone