Association between Exposure to Estrogenic Endocrine Disruptors - Polychlorinated Biphenyls, Phthalates, and Bisphenol A and Gynecologic Cancers- Cervical, Ovarian, Uterine Cancers

Abstract

Introduction: Estrogen is a driver in the growth and progression of gynecologic cancers (cervical, ovarian, and uterine). A number of estrogenically active chemicals are suspected to contribute in the development of gynecologic lesions, including an increased risk of estrogen-dependent cancer in women. Humans are exposed to estrogenic endocrine disruptors (EEDs), such as- polychlorinated biphenyls (PCBs), phthalates and bisphenol A (BPA). Therefore, we examined the cross-sectional relationship between exposure to PCBs, phthalates, and BPA and gynecologic cancers (cervical, ovarian, and uterine). Methods: We analyzed data from female participants (20 years of age and older) who provided blood and urine samples for the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. Exposure was examined based on lipid adjusted serum levels of 6 individual PCB congeners (74, 99, 118, 138, 153, and 180), the sum of dioxin-like PCBs (074 and 118), the sum of non-dioxin-like PCBs (099+138+153+187), 8 urinary phthalate metabolites (MNP, MEP, MEHP, MBzP, MCPP, MEHHP, MEOHP, and MIB), the sum of DEHP metabolites (MHP+MHH+MOH), the sum of total phthalates, and urinary BPA in conjunction with data obtained from the medical and reproductive health questionnaires. We calculated geometric means to compare EEDs concentrations in women who self-reported a cervical, ovarian, or uterine cancer diagnosis vs. women who self-reported never being diagnosed with cancer. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between exposure to EEDs and r gynecologic cancers. We also evaluated age, race/ethnicity, body mass index (BMI; kg/m2), and age at menarche as potential confounding variables in our final models. Results: Separate analyses showed weighted geometric mean (GM) levels of individual PCB congeners to be significantly higher among women with ovarian cancer, and uterine cancer when compared to the rest of the study population. Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was found to be significantly higher and BPA was higher among women with ovarian cancer compared to women never diagnosed with any gynecologic cancer. After adjusting for age, race, BMI, and age at menarche, we found that PCB 138 was significantly associated with cervical cancer, and uterine cancer [odds ratios of 3.05, 95% CI: 1.21-7.69; and 5.83, 95% CI: 1.63-20.9], respectively. PCB 74 and 118 however, were significantly associated with ovarian cancer with an odds ratios of 6.47, 95% CI: 1.23-3.41 (for PCB 74) and 6.68, 95% CI: 1.39-32.3 (for PCB 118). We also found the sum of non-dioxin-like PCBs to be significantly associated with uterine cancer (OR of 1.12, 95% CI: 1.03-1.23) and the sum of dioxin-like PCBs to be significantly associated with ovarian cancer (OR of 2.02, 95% CI: 1.06-3.85). We did not find significant associations between urinary phthalates and BPA and gynecologic cancers. Conclusions: Our findings point to a possible association between environmental exposure to PCBs and an increased risk of cervix, ovarian and uterine cancer. However, these findings should be interpreted cautiously because of self-reported cross sectional data and a limited sample size of gynecologic cancers.