Abstract

Abstract Background: Whilst unopposed estrogen exposure is considered the major driver of endometrial carcinogenesis, inflammation and insulin resistance/hyperinsulinemia are major biological pathways that increase the risk of endometrial cancer. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of type 1 endometrial cancer. Methods: We prospectively followed 48,526 women from the Nurses’ Health Study (NHS, 1984-2016) and 87,323 women from the Nurses’ Health Study II (NHS II, 1989-2017). Using repeated measures of food frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide, respectively. Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CIs) for type 1 endometrial cancer risk. Results: We documented 1,468 type 1 endometrial cancer cases over 2,544,615 person-years of follow-up. Diets with higher inflammatory or insulinemic potential were associated with increased risk of type 1 endometrial cancer in the Nurses’ Health Studies. In the pooled multivariable-adjusted analyses, women in the highest EDIP or EDIH quintile had 1.66 times (HR, 1.66; 95% CI, 1.40-1.97) and 1.57 times (HR, 1.57; 95% CI, 1.33-1.86) higher risk of type 1 endometrial cancer, respectively, compared to women in the lowest quintile. However, additional adjustment for body mass index (BMI) attenuated the associations (HR, 1.15; 95% CI, 0.96-1.37 for EDIP; HR, 1.02; 95% CI, 0.85-1.21 for EDIH), suggesting adiposity may mediate the association of these dietary indices with type 1 endometrial cancer risk. In subgroup analyses, we observed a significant interaction by BMI (P-interaction<0.01), where a significant direct association with EDIP was evident in women with BMI between 27 and 30 (HRQ5vs.Q1 1.47; 95% CI 0.92, 2.35; p-trend=0.02), but not among normal weight or obese women. Further adjusting for continuous BMI did not change the scenario (HRQ5vs.Q11.44; 95% CI 0.90, 2.30). Conclusions: We found that higher dietary inflammatory or insulinemic potential was associated with increased type 1 endometrial cancer incidence, nonetheless this association was not independent of adiposity. Furthermore, among overweight women, greater EDIP was directly associated with risk, even after adjusting for BMI. Citation Format: Andrea Romanos-Nanclares, Fred K. Tabung, Jennifer Sinnott, Britton Trabert, Immaculata De Vivo, Mary C. Playdon, A. Heather Eliassen. Inflammatory and insulinemic dietary patterns and risk of endometrial cancer: Results from two prospective US cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 16.

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