INVESTIGATIONS OF THE ROLE OF ACCULTURATION IN CANCER SCREENING AND PHTHALATES IN BREAST CANCER RISK AND WEIGHT AND BODY MASS INDEX CHANGE MAY 2018 MARY V. DIAZ SANTANA, B.S., UNIVERSITY OF PUERTO RICO RIO PIEDRAS CAMPUS M.S., UNIVERSITY OF PUERTO RICO MEDICAL SCIENCE CAMPUS Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Katherine Reeves Phthalates, endocrine-disrupting chemicals, are hypothesized to increase obesity and, as a result, risk of obesity-related cancers, such as breast cancer. However, findings are not consistent across studies. Identifying whether phthalates impact obesity is critical for understanding the pathways by which phthalates may affect cancer risk. Experimental evidence supports the potentially carcinogenic effects of phthalates. However, prospective data on whether phthalates affect human breast cancer risk is lacking. In study 1) We conducted a case-control study nested within the Women’s Health Initiative (WHI) prospective cohort. Urinary levels of thirteen PMs were measured. Conditional logistic regression analysis was used to estimate risk ratios and 95% confidence intervals for breast cancer risk associated with each phthalate metabolites (PM). We observed null associations between individual PMs and breast cancer risk. Additionally, a significant inverse association with two metabolites was observed: e.g., monohydroxy-isobutyl phthalate (RR 0.66, 95% CI 0.46-0.94) for 4th quartile (Q4) vs. 1st quartile (Q1). These results indicate that urinary PM levels are not related to increased breast cancer risk. However, some PMs may be associated with decreased risk, possibly through anti-estrogenic actions. Future analyses should assess the phthalates concentration during windows of susceptibility more relevant in breast carcinogenesis. In study 2) We performed a cross-sectional and prospective analysis of the1, 257 women that participated in study 1. Urinary levels of thirteen PMs were measured. Study personnel measured participants’ weight and height at baseline and during follow. Linear, multinominal logistic regression and mixed model analysis was used to estimate associations between each PM, and weight and body mass index (BMI). Compared to women in the Q1 of the PM’s distribution, those in the Q4 were more likely to be obese: e.g., mono-carboxyoctyl phthalate (OR 2.62, 95%CI 1.51-4.56). After three years of follow up, women in the Q4 of the MEP had an increase in BMI of 0.44 kg/m2 compared to women in the Q1 of the PM’s distribution. We observed positive associations between PMs and obesity in the cross-sectional and longitudinal analyses these findings suggest that environmental exposure to PMs may be relevant to the ongoing obesity epidemic.