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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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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.


Funder: World Cancer Research Fund (WCRF UK); doi:

Funder: Vetenskapsrådet (Swedish Research Council); doi:

Funder: Crafoordska Stiftelsen (Crafoord Foundation); doi:

Funder: Swedish Prostate Cancer Federation Märta Winkler Foundation

Funder: Cancerfonden (Swedish Cancer Society); doi:

Funder: Forskningsrådet om Hälsa, Arbetsliv och Välfärd (Swedish Research Council for Health, Working Life and Welfare); doi:


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

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Br J Cancer

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Springer Science and Business Media LLC