Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women

Abstract

Breast cancer risk is higher in US-born than in foreign-born Hispanics/Latinas and also increases with greater length of US residency. It is only partially known what factors contribute to these patterns of risk. To gain new insights, we tested the association between lifestyle and demographic variables and breast cancer status, with measures of estrogenic (E) and glucocorticogenic (G) activity in Mexican American women. We used Chemical-Activated LUciferase gene eXpression assays to measure E and G activity in total plasma from 90 Mexican American women, without a history of breast cancer at the time of recruitment, from the San Francisco Bay Area Breast Cancer Study. We tested associations of nativity, lifestyle and sociodemographic factors with E and G activity using linear regression models. We did not find a statistically significant difference in E or G activity by nativity. However, in multivariable models, E activity was associated with Indigenous American ancestry (19% decrease in E activity per 10% increase in ancestry, P = 0.014) and with length of US residency (28% increase in E activity for every 10 years, P = 0.035). G activity was associated with breast cancer status (women who have developed breast cancer since recruitment into the study had 21% lower G activity than those who have not, P = 0.054) and alcohol intake (drinkers had 25% higher G activity than non-drinkers, P = 0.015). These associations suggest that previously reported breast cancer risk factors such as genetic ancestry and alcohol intake might in part be associated with breast cancer risk through mechanisms linked to the endocrine system.

Cell‐Based Bioassay to Screen Environmental Chemicals and Human Serum for Total Glucocorticogenic Activity

“…Although both of these techniques quantify the amount of a specific compound present in a biospecimen, they often require sample preparation, are expensive, and do not measure the biological effect of exogenous and endogenous compounds present in serum (Xu et al 2014). Alternatively, several studies thus far have used cell‐based bioassays to detect differences in serum TGA (Raivio et al 2002; Vermeer et al 2003; Kajantie et al 2004; Turner et al 2010; Perogamvros et al 2011; Fejerman et al 2016). For example, elevated serum TGA was detected after synthetic glucocorticoid administration (Raivio et al 2002).…”

“…A similar protocol was used to screen human serum with MDA‐Kb2 cells for comparison with 231GRE results. Details of this assay are described in Fejerman et al (2016). Because the androgen receptor is highly expressed in MDA‐Kb2 cells, treatments were performed in the presence of the androgen receptor antagonist hydroxyflutamide, to distinguish between androgenic and glucocorticogenic activity.…”

“…A luciferase reporter model is frequently used because the assay is rapid, simple, relatively inexpensive, sensitive, and has a broad linear range (Smale 2010). Not only has this technology helped to identify chemicals that interfere with receptor‐mediated effects, but studies have also demonstrated that glucocorticoid receptor bioassays can quantify total glucocorticogenic activity (TGA) in human serum and plasma (Raivio et al 2002; Vermeer et al 2003; Kajantie et al 2004; Turner et al 2010; Perogamvros et al 2011; Fejerman et al 2016). Although these studies highlight that cell‐based bioassays can be used to detect differences in serum TGA, they are not without limitations.…”

Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches

“…T47D-KBluc cells were cultured in DMEM with 10% FBS until 1 week prior to the experiment as previously described with minor modifications 47 . Cells were seeded at a density of 3.0 × 10 4 cells/well in white, 96-well microtiter plates (Thermo Scientific, Grand Island, NY, USA).…”

Estrogenic activity, race/ethnicity, and Indigenous American ancestry among San Francisco Bay Area women

“…Various methods are available to quantify estrogen receptor (ER) function and activation. Luciferase assays have been widely used and have proven useful in predicting breast cancer risk [ 18 ], [ 19 ]. Generally, due to the fluctuations of estrogens throughout the menstrual cycle, estrogen measures have been more consistent for postmenopausal than premenopausal women [ 20 ].…”