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Thesis
Peer Reviewed

Hormone Receptor Activity and Chronic Disease Risk in Migrant Populations

Sanchez, Sylvia S
Advisor(s): Smith, Martyn T

UC Berkeley Electronic Theses and Dissertations (2019)

Non-communicable diseases (NCDs), including type 2 diabetes (T2D) and breast cancer, account for a vast majority of deaths worldwide. The incidence rates of these morbidities vary widely among different ethnic groups with racial minorities disproportionately affected by these chronic pathologies. Known risk factors among those afflicted with T2D and breast cancer include genetic markers, diet, obesity, and other lifestyle factors. However, these risk factors cannot fully explain the observed incidence rates across different ethnic populations. For migrant populations whose environment is often altered throughout their lifetime, environmental factors play a significant role in the development of chronic diseases. For this reason, approaches that are aimed at identifying non-genetic factors are necessary. This dissertation makes use of an exposome approach known as the receptorome. This methodology was used to investigate differences in hormone receptor activity and their association to breast cancer and T2D in migrant populations. The introduction in Chapter 1 provides an overview of the exposome approach highlighting the role of steroid hormones and environmental mimics in the development of two chronic diseases that disproportionately affect migrant populations. Chapter 2 investigates the association between estrogenic activity and nativity, genetic ancestry, and lifestyle factors among Mexican women. Chapter 3 is an extension of the previous chapter, providing further evidence that ancestry and other breast cancer risk factors may be associated with mechanisms linked through the endocrine system. This study demonstrates the importance of endogenous and exogenous estrogens among different racial/ethnic groups and their potential role in breast cancer incidence rates. Chapter 4 examines hormone receptor activity and the association to T2D and persistent organic pollutants in South Indian Asians and European Whites living in London. Lastly, Chapter 5 summarizes all findings and elucidates a secondary technique, known as metabolomics, to aid in the identification of novel environmental risk factors affecting the incidence rates of NCDs in migrant groups.

Cover page: Hormone Receptor Activity and Chronic Disease Risk in Migrant Populations

Article
Peer Reviewed

Plasma glucocorticogenic activity, race/ethnicity and alcohol intake among San Francisco Bay Area women

UC Davis Previously Published Works (2020)

Racial and ethnic minorities are at higher risk for a variety of diseases. While sociodemographic and lifestyle factors contribute to racial/ethnic health disparities, the biological processes underlying these associations remain poorly understood. Stress and its biological consequences through the glucocorticoid receptor (GR) have been hypothesized to mediate adverse disease outcomes. In fasting morning samples of 503 control women from the San Francisco Bay Area Breast Cancer Study, we used a sensitive Chemical-Activated LUciferase gene eXpression (CALUX) assay to examine the association of sociodemographic and lifestyle factors with plasma glucocorticogenic (G) activity in three racial/ethnic groups. The G activity is a sensitive measure that reflects biological activity of total plasma glucocorticoids including cortisol and glucocorticoid-like compounds. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression models. Latina and non-Latina Black (NLB) women had 9% (P = 0.053) and 14% (P = 0.008) lower morning G activity than non-Latina White (NLW) women, respectively. Additionally, we replicated a previously reported association between G activity and alcohol intake (women who drank >10gms had 19% higher G activity than non-drinkers, P = 0.004) in Latina and NLB women. Further research should assess the association between G activity and health outcomes in a prospective cohort so as to characterize the relationship between total plasma G activity in pre-disease state and disease outcomes across different racial/ethnic populations.

Article
Peer Reviewed

Plasma glucocorticogenic activity, race/ethnicity and alcohol intake among San Francisco Bay Area women

UC Davis Previously Published Works (2020)

Racial and ethnic minorities are at higher risk for a variety of diseases. While sociodemographic and lifestyle factors contribute to racial/ethnic health disparities, the biological processes underlying these associations remain poorly understood. Stress and its biological consequences through the glucocorticoid receptor (GR) have been hypothesized to mediate adverse disease outcomes. In fasting morning samples of 503 control women from the San Francisco Bay Area Breast Cancer Study, we used a sensitive Chemical-Activated LUciferase gene eXpression (CALUX) assay to examine the association of sociodemographic and lifestyle factors with plasma glucocorticogenic (G) activity in three racial/ethnic groups. The G activity is a sensitive measure that reflects biological activity of total plasma glucocorticoids including cortisol and glucocorticoid-like compounds. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression models. Latina and non-Latina Black (NLB) women had 9% (P = 0.053) and 14% (P = 0.008) lower morning G activity than non-Latina White (NLW) women, respectively. Additionally, we replicated a previously reported association between G activity and alcohol intake (women who drank >10gms had 19% higher G activity than non-drinkers, P = 0.004) in Latina and NLB women. Further research should assess the association between G activity and health outcomes in a prospective cohort so as to characterize the relationship between total plasma G activity in pre-disease state and disease outcomes across different racial/ethnic populations.

Article
Peer Reviewed

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

UC Berkeley Previously Published Works (2019)

Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk.

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

Article
Peer Reviewed

Elevated Levels of Organochlorine Pesticides in South Asian Immigrants Are Associated With an Increased Risk of Diabetes

UC Davis Previously Published Works (2018)

Objective

Rates of diabetes mellitus are higher in South Asians than in other populations and persist after migration. One unexplored cause may be higher exposure to persistent organic pollutants associated with diabetes in other populations. We compared organochlorine (OC) pesticide concentrations in South Asian immigrants and European whites to determine whether the disease was positively associated with OC pesticides in South Asians.

Research design and methods

South Asians of Tamil or Telugu descent (n = 120) and European whites (n = 72) were recruited into the London Life Sciences Population Study cohort. Blood samples as well as biometric, clinical, and survey data were collected. Plasma levels of p,p'-dichlorodiphenyldichloroethylene (DDE), p,p'- dichlorodiphenyltrichloroethane, β-hexachlorohexane (HCH), and polychlorinated biphenyl-118 were analyzed by gas chromatography-mass spectrometry. South Asian cases and controls were categorized by binary exposure (above vs below the 50th percentile) to perform logistic regression.

Results

Tamils had approximately threefold to ninefold higher levels of OC pesticides, and Telugus had ninefold to 30-fold higher levels compared with European whites. The odds of exposure to p,p'-DDE above the 50th percentile was significantly greater in South Asian diabetes cases than in controls (OR: 7.00; 95% CI: 2.22, 22.06). The odds of exposure to β-HCH above the 50th percentile was significantly greater in the Tamil cases than in controls (OR: 9.35; 95% CI: 2.43, 35.97).

Conclusions

South Asian immigrants have a higher body burden of OC pesticides than European whites. Diabetes mellitus is associated with higher p,p'-DDE and β-HCH concentrations in this population. Additional longitudinal studies of South Asian populations should be performed.

Cover page: Elevated Levels of Organochlorine Pesticides in South Asian Immigrants Are Associated With an Increased Risk of Diabetes