Date of Conferral

2016

Degree

Ph.D.

School

Public Health

Advisor

Amy Thompson

Abstract

Synthetic xenoestrogens have differential estrogenic properties. Research has shown that exposures to xenoestrogens could promote breast cancer by disrupting normal function of the human epidermal growth factor receptor 2 (Her2) gene. Although animal models demonstrated a connection between xenoestrogen exposure and Her2 activity, no study using human cells has systematically examined their carcinogenic potential influencing the Her2 gene expression. Furthermore, breast cancer cells are phenotypically disparate (ER+, Her2+), with some phenotypes (Her2+), leading to more aggressive disease. This study aimed to dosimetrically assess the carcinogenic potential of commonly used xenoestrogens influencing Her2 gene expression, and delineate cellular phenotypes at greater risk of more aggressive disease. The study assessed whether the composition, concentrations, and exposure duration of BPA, EE, NPH, and DDT significantly altered Her2 copy numbers in estrogen and Her2 receptor positive or negative breast cancer lines. Each line was randomly assigned to cases (exposed) and control (unexposed) groups using a randomized block design. Fluorescent in-situ hybridization measured Her2 gene copies. Mann Whitney, Kruskal Wallis, and Incidence Rate Ratios revealed Her2 copy gains in all 4 xenoestrogens and receptor types with persistent exposures. A 44% increase in Her2 was observed in the normal ER and Her2 line, marking a shift in its Her2 status, and a 30-times greater risk was noted in the Her2+ lines. These findings promote positive social change by revealing all 4 xenoestrogens as risk factors for breast cancer. This information can be used by breast cancer advocacy groups, health educators, and steering committees to educate women and formulating policies.

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