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Body mass index, triglyceride-glucose index, and prostate cancer death: a mediation analysis in eight European cohorts
Department of Translational Medicine, Lund University, Malmö, Sweden; Institute of Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria.
Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
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2024 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 130, p. 308-316Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2024. Vol. 130, p. 308-316
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Cancer and Oncology
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URN: urn:nbn:se:umu:diva-218306DOI: 10.1038/s41416-023-02526-1ISI: 001124661600001PubMedID: 38087039Scopus ID: 2-s2.0-85179305097OAI: oai:DiVA.org:umu-218306DiVA, id: diva2:1822145
Funder
World Cancer Research Fund InternationalSwedish Cancer Society, 20 1033 PjFSwedish Cancer Society, CAN 2017/1019Swedish Research Council, 2018-02825ProstatacancerförbundetThe Crafoord Foundation, 20200546Available from: 2023-12-21 Created: 2023-12-21 Last updated: 2024-04-26Bibliographically approved

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Häggström, ChristelHarlid, Sophia

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