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Body mass index, triglyceride-glucose index, and prostate cancer death: a mediation analysis in eight European cohorts.

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Peer-reviewed

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Abstract

BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

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Funder: World Cancer Research Fund (WCRF UK); doi: https://doi.org/10.13039/501100000321


Funder: Vetenskapsrådet (Swedish Research Council); doi: https://doi.org/10.13039/501100004359


Funder: Crafoordska Stiftelsen (Crafoord Foundation); doi: https://doi.org/10.13039/501100003173


Funder: Swedish Prostate Cancer Federation Märta Winkler Foundation


Funder: Cancerfonden (Swedish Cancer Society); doi: https://doi.org/10.13039/501100002794


Funder: Forskningsrådet om Hälsa, Arbetsliv och Välfärd (Swedish Research Council for Health, Working Life and Welfare); doi: https://doi.org/10.13039/501100006636

Keywords

Male, Humans, Body Mass Index, Mediation Analysis, Insulin Resistance, Prostatic Neoplasms, Glucose, Obesity, Triglycerides, Blood Glucose, Risk Factors, Biomarkers

Journal Title

Br J Cancer

Conference Name

Journal ISSN

0007-0920
1532-1827

Volume Title

130

Publisher

Springer Science and Business Media LLC