Premenopausal and postmenopausal obesity and endometrial cancer risk: circulating biomarkers of inflammation, insulin resistance, and sex hormones as mediators.

Cancer research · Endometrial cancer

Circulating biomarkers for inflammation, insulin resistance, and sex hormones may mediate the effect of obesity on endometrial cancer risk, with some overlaps in mediating pathways. Sex hormones were the most prominent mediators in postmenopausal obesity, whereas biomarkers for inflammation may play an important role in premenopausal obesity.

Within the European Prospective Investigation into Cancer and Nutrition cohort, prediagnostic circulating biomarkers were examined in 337 postmenopausal and 196 premenopausal matched case‑control pairs to investigate mediation of the obesity–endometrial cancer relationship. The adjusted OR for obesity versus BMI<25kg/m² was 3.34 (CI 1.97–5.65) postmenopausal and 3.24 (CI 1.43–7.36) premenopausal. Joint mediation through all biomarkers yielded an ORNIE of 1.82 (CI 1.21–2.74; 50 % mediated) postmenopausal and 1.79 (CI 0.97–3.29; 49 % mediated) premenopausal. Sequentially, estrone (ORNIE = 1.20; CI 1.02–1.41; 15 % mediated) and interleukin‑6 (ORNIE = 1.35; CI 1.03–1.78; 24 % mediated) were key mediators in post‑ and pre‑menopausal analyses, respectively.

Understanding how obesity contributes to endometrial cancer risk through specific biological pathways can inform prevention strategies and identify potential therapeutic targets.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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