Abstract PR05: Estrogenic activity is associated with race/ethnicity and Indigenous American ancestry among San Francisco Bay Area women
Authors: Sanchez Sylvia S. , Tachachartvanich Phum , Ruiz Heather , Stanczyk Frank Z. , Gomez Scarlett Lin , John Esther M. , Smith Martyn T. , Fejerman Laura 
Published: February 2019

Abstract
The incidence of breast cancer in the U.S. varies by race/ethnicity. Furthermore, in Hispanic women, breast cancer risk is higher among women with low Indigenous American ancestry compared to those with high Indigenous American ancestry and in U.S.-born compared to foreign-born women. In a previous pilot study among foreign-born and U.S.-born Mexican women, we found that plasma estrogenic (E) activity was associated with genetic ancestry and years of U.S. residence, suggesting the possibility of a hormone-related pathway for the observed differences in breast cancer risk. In the present study, we examined the association between E activity and genetic ancestry in a larger sample of Hispanic women. We also evaluated the association between E activity, demographic factors, and breast cancer risk in non-Hispanic Black (NHB) and non-Hispanic White (NHW) women. We utilized a receptor-mediated Chemical-Activated Luciferase gene eXpression (CALUX) assay for the assessment of total activity profiles against estrogen receptors (ER) in human plasma, which captures levels of both endogenous and exogenous estrogenic compounds. Results were expressed in relative light units (RLUs), with higher RLU values reflecting greater E activity in plasma. ER activation was measured in plasma samples of 329 Hispanic, 100 NHBs, and 74 NHW women who participated as controls in the San Francisco Bay Area Breast Cancer Study (SFBCS). The participants ranged in age from 35 to 79 years, though the study was composed predominantly of postmenopausal women. Multivariable regression models included race/ethnicity, age at blood draw, height, body mass index (BMI), neighborhood socioeconomic status (SES), and alcohol intake. In the univariate model that included all women (n=503) and race/ethnicity as the independent predictor, Hispanics had 24% lower E activity (p=0.061) and NHBs had 36% higher activity (p=0.047) compared to NHWs. In the multivariable model, Hispanics still showed lower E activity levels (34%, p=0.009), but the difference with NHBs and NHWs was no longer statistically significant (p=0.493). After adjustment for levels of two endogenous estrogens, estradiol and estrone, in a subset of samples (n=260), Hispanics continued to show 20% lower E activity compared to NHWs. In addition, when BMI is categorized into tertiles consisting of normal (&lt;25 kg/m2), overweight (25-30 kg/m2), and obese (BMI &gt;30 kg/m2) women, we found that obese women had 73% higher E activity compared to those with normal BMI (p&lt;0.001) and overweight women had 46% higher activity (p=0.006). Among the Hispanic women, we confirmed the previously observed negative association between E activity and Indigenous American ancestry, which is consistent with the observation that Hispanic women with high Indigenous American ancestry have lower risk of developing breast cancer. Overall, our study suggests that observed associations between race/ethnicity, genetic ancestry and BMI with breast cancer risk could be partly due to the mediating effect of endogenous estrogens as well as to the effect of exogenous estrogen-like compounds.
Citation Format: Sylvia S. Sanchez, Phum Tachachartvanich, Heather Ruiz, Frank Z. Stanczyk, Scarlett Lin Gomez, Esther M. John, Martyn T. Smith, Laura Fejerman. Estrogenic activity is associated with race/ethnicity and Indigenous American ancestry among San Francisco Bay Area women [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR05.