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

Ekedahl, Henrik LU ; Isaksson, Sigrid LU ; Ståhl, Olof LU ; Bogefors, Karolina LU ; Romerius, Patrik LU ; Eberhard, Jakob LU and Giwercman, Aleksander LU (2022) In BMC Cancer 22. p.1-11
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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adolescent, Adult, Cancer Survivors/statistics & numerical data, Cardiometabolic Risk Factors, Follow-Up Studies, Humans, Hypogonadism/blood, Inflammation, Inflammation Mediators/blood, Interleukin-10/blood, Interleukin-6/blood, Logistic Models, Male, Metabolic Syndrome/blood, Middle Aged, Odds Ratio, Testicular Neoplasms/blood, Testosterone/blood, Young Adult
in
BMC Cancer
volume
22
article number
157
pages
1 - 11
publisher
BioMed Central (BMC)
external identifiers
  • pmid:35135482
  • scopus:85124269694
ISSN
1471-2407
DOI
10.1186/s12885-022-09253-5
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
a5fcb875-96bc-44f8-a7e9-dc4e6f176a1c
date added to LUP
2022-05-01 07:47:33
date last changed
2024-11-29 07:01:18
@article{a5fcb875-96bc-44f8-a7e9-dc4e6f176a1c,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Ekedahl, Henrik and Isaksson, Sigrid and Ståhl, Olof and Bogefors, Karolina and Romerius, Patrik and Eberhard, Jakob and Giwercman, Aleksander}},
  issn         = {{1471-2407}},
  keywords     = {{Adolescent; Adult; Cancer Survivors/statistics & numerical data; Cardiometabolic Risk Factors; Follow-Up Studies; Humans; Hypogonadism/blood; Inflammation; Inflammation Mediators/blood; Interleukin-10/blood; Interleukin-6/blood; Logistic Models; Male; Metabolic Syndrome/blood; Middle Aged; Odds Ratio; Testicular Neoplasms/blood; Testosterone/blood; Young Adult}},
  language     = {{eng}},
  pages        = {{1--11}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Cancer}},
  title        = {{Low-grade inflammation in survivors of childhood cancer and testicular cancer and its association with hypogonadism and metabolic risk factors}},
  url          = {{http://dx.doi.org/10.1186/s12885-022-09253-5}},
  doi          = {{10.1186/s12885-022-09253-5}},
  volume       = {{22}},
  year         = {{2022}},
}