Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
Cancer Epidemiol Biomarkers Prev. 2021 Jan;30(1):104-113. doi: 10.1158/1055-9965.EPI-20-0965. Epub 2020 Oct 2.
Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women.
We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis.
The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m was 2.51 (95% confidence interval, 1.26-5.02). The ORs were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The OR not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results.
Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight.
If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
肥胖会增加子宫内膜癌的风险，这可能是通过炎症、高胰岛素血症和雌激素增加来实现的。我们旨在量化脂联素（抗炎脂肪细胞因子）；IL6、IL1 受体拮抗剂、TNF 受体 1 和 2 以及 C 反应蛋白（炎症状态生物标志物）；C 肽（高胰岛素血症生物标志物）；以及游离雌二醇和雌酮（雌激素生物标志物）在绝经后妇女肥胖与子宫内膜癌之间的中介作用。
我们使用了欧洲癌症与营养前瞻性调查（EPIC）中的一项病例对照研究的数据。合格的女性没有癌症、子宫切除术和糖尿病；在招募时没有服用口服避孕药或激素疗法；并且绝经后。通过估计自然间接（NIE）和直接（NDE）效应，使用序贯中介分析来研究从肥胖到子宫内膜癌的中介途径。
该研究包括 163 例病例和 306 例对照。体重指数（BMI）≥30 与≥18.5-<25 kg/m2 相比，子宫内膜癌的调整比值比（OR）为 2.51（95%置信区间，1.26-5.02）。通过所有生物标志物的 OR 为 1.95（1.01-3.74）[72%的比例（PM）分解为]：通过脂联素起源的途径（33%的 PM）为 1.35（1.06-1.73）；通过脂联素和炎症之外的炎症（13%的 PM）为 1.13（0.71-1.80）；通过 C 肽超过脂联素和炎症（5%的 PM）为 1.05（0.88-1.24）；通过雌激素超过先前的生物标志物（21%的 PM）为 1.22（0.89-1.67）。不通过生物标志物的 OR 为 1.29（0.54-3.09）。腰围得出了类似的结果。
肥胖女性中，脂联素减少和炎症生物标志物、C 肽和雌激素增加约解释了 70%的子宫内膜癌发病风险增加。
如果得到复制，这些结果可能对确定肥胖女性子宫内膜癌风险降低的干预目标具有重要意义。
