Abstract PO-163: Pre-diagnostic phthalates and other endocrine disruptors in relation to endometrial cancer risk in the Multiethnic Cohort (MEC) Study

Abstract

Abstract Introduction: Endometrial cancer develops under conditions of high circulating estrogen levels unopposed by progesterone. We hypothesized that exposure to endocrine disrupting chemicals (EDCs), including those that are used in plastics such as phthalates, will increase endometrial cancer risk and may contribute to racial/ethnic differences in risk. Methods: We conducted a case-control study nested in the Multiethnic Cohort (MEC) Study to measure EDCs in pre-diagnostic urine samples. We identified 139 postmenopausal endometrial cancer cases and 139 female controls matched on race/ethnicity, study site, birth year, fasting hours, urine type, date/time of urine collection and current menopausal hormone therapy use. Concentrations of 17 EDCs including urinary phthalates, bisphenol A, parabens and triclosan were measured by highly sensitive liquid chromatography high-resolution accurate-mass mass spectrometry in the UHCC Analytical Biochemistry Shared Resource using validated published protocols. Creatinine-adjusted urinary EDC excretion values were divided into tertiles based on the distribution in controls. Conditional logistic regression, with matched sets used as strata, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between EDC levels and endometrial cancer risk accounting for body mass index (BMI), diabetes, and the Mediterranean Diet Score. Results: The median (Q25, Q75) time between urine collection and endometrial cancer diagnosis was 6.6 years (3.4, 9.4). Fifty-two case-control sets were Japanese American, 35 were White, 26 were Native Hawaiian, 17 were Latina and nine were African American. In analyses of the full population, the butyl phthalate metabolite monoisobutyl phthalate (MIBP) was suggestively associated with endometrial cancer risk (tertile 3 (T3) vs. T1, OR 2.07 [CI 0.96-4.47]). This association was stronger in non-whites (n=104 case-sets; T3 vs. T1, OR 3.11 [CI 1.17-8.27]), who are thought to be exposed to higher levels of selected EDCs. We also observed a non-significant positive association among non-whites for mono n-butyl phthalate (MBP; T3 vs. T1, OR 2.55 [CI 0.90-7.22]). Conclusion: To our knowledge this is the first study to examine the role of several EDCs in relation to endometrial cancer risk using pre-diagnostic samples. These data suggest that exposure to di-butyl phthalates, which were observed in vitro to be weakly estrogenic in mammalian estrogen screens (Jobling et al., 1995, Environ Health Perspect, 103: 582-7), may represent a risk factor for endometrial cancer among non-white women that is independent of BMI and diabetes status. Replication of these findings in other large cohort studies is warranted, especially in non-whites. Citation Format: Danja Sarink, Loïc Le Marchand, Iona Cheng, Anna H. Wu, Adrian A. Franke, Lynne R. Wilkens, Kami K. White, Herbert Yu, Melissa A. Merritt. Pre-diagnostic phthalates and other endocrine disruptors in relation to endometrial cancer risk in the Multiethnic Cohort (MEC) Study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-163.