Metabolic syndrome biomarkers and prostate cancer risk in the UK Biobank

TY - JOUR

T1 - Metabolic syndrome biomarkers and prostate cancer risk in the UK Biobank

AU - Monroy Iglesias, Maria

AU - Russell, Beth

AU - Crawley, Danielle

AU - Allen, Naomi

AU - Travis, Ruth

AU - Perez-Cornago, Aurora

AU - Van Hemelrijck, Mieke

AU - Beckmann, Kerri

N1 - Funding Information: Kerri Beckmann was supported by a National Health and Medical Research Council Early Career Researcher Fellowship (Australia) GNT1124210. Aurora Perez‐Cornago is supported by a Cancer Research UK Population Research Fellowship (C60192/A28516) and by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (2019/1953). Ruth C. Travis was supported by Cancer Research UK (grant numbers C8221/A19170 and C8221/A29017). Funding Information: Cancer Research UK, Grant/Award Numbers: C8221/A29017, C8221/A19170; World Cancer Research Fund (WCRF UK), Grant/Award Number: 2019/1953; Cancer Research UK Population Research Fellowship, Grant/Award Number: C60192/A28516; National Health and Medical Research Council Early Career Researcher Fellowship (Australia), Grant/Award Number: GNT1124210 Funding information Publisher Copyright: © 2020 Union for International Cancer Control Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2/15

Y1 - 2021/2/15

N2 - 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.

AB - 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.

KW - glycated hemoglobin

KW - mediation analysis

KW - metabolic syndrome

KW - prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85090575726&partnerID=8YFLogxK

U2 - 10.1002/ijc.33255

DO - 10.1002/ijc.33255

M3 - Article

AN - SCOPUS:85090575726

SN - 0020-7136

VL - 148

SP - 825

EP - 834

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 4

ER -