4.7 Article

Metabolic syndrome biomarkers and prostate cancer risk in theUKBiobank

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 148, Issue 4, Pages 825-834

Publisher

WILEY
DOI: 10.1002/ijc.33255

Keywords

glycated hemoglobin; mediation analysis; metabolic syndrome; prostate cancer

Categories

Funding

  1. Cancer Research UK [C8221/A29017, C8221/A19170]
  2. World Cancer Research Fund (WCRF UK) [2019/1953]
  3. Cancer Research UK Population Research Fellowship [C60192/A28516]
  4. National Health and Medical Research Council Early Career Researcher Fellowship (Australia) [GNT1124210]

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The study found no significant association between Metabolic Syndrome (MetS) and risk of prostate cancer (PCa), but a consistent inverse association was observed with the blood sugar indicator HbA1c. Mediation analysis revealed potential hormonal and inflammatory pathways which may influence this association.
We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (>= 42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.

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