[This page is intended to provide a study summary, the sections of which are below. Please complete these sections, as applicable. The headings below are suggested headings. You can remove inapplicable sections, or add new ones relevant to your study]
Investigator Names and Contact Information
Juhua Luo, PhD and Katherine W. Reeves
Emerging evidence documents that BPA, a chemical used in the production of many plastics and epoxy resins, is an endocrine disruptor.1 Exposure to BPA is highly prevalent,2and occurs primarily through leaching of BPA from plastic containers and cans into food and liquids that are subsequently ingested.1 There are significant concerns that exposure to BPA could increase risk of a variety of poor health outcomes, including miscarriage, polycystic ovarian syndrome, diabetes, and cancer.1 Though in vitro data present convincing evidence for a role of BPA in breast cancer promotion,3-9 no epidemiological studies have evaluated the hypothesis that BPA exposure is associated with increased breast cancer risk in general populations.
In humans, BPA is rapidly absorbed and eliminated as glucuronide or sulfate conjugates in urine with a terminal half-life of less than 6 h following oral administration, and recovered completely in urine approximately 24 h after administration.10 Because of the rapid and complete renal elimination of absorbed BPA, the total (free plus conjugated) BPA urinary concentration becomes a widely used biomarker of BPA exposure in population-based biomonitoring studies.11 However, because of the ubiquitous presence of BPA in the environment even in indoor air and dust,12, 13 there is a special concern of potential contamination with trace levels of free BPA.14, 15
The WHI is a well-known large prospective study with a rigorous standard protocol in sample collection, handling and storage. Regarding urine samples, the WHI recommended urine collection containers and centrifuge tubes with no BPA. However, it was up to individual clinics to decide what collection containers and tubes to use, and it is possible that some clinics used containers or centrifuge tubes that contained BPA. Furthermore, BPA is such an omnipresent environmental contaminant and we are using archived human specimens that had not been specifically collected for measuring BPA. Thus, a pilot study is needed to first ensure the integrity of the specimen before proposing to conduct a large study.
In addition, the within-person variability of BPA is high,18-20 complicating accurate classification of exposure. Prior to undertaking a nested case-control study, we need to ensure that our exposure measurement will allow us to provide a valid test of our hypothesis. Improved classification of BPA may be achieved by incorporating BPA levels from multiple time points, though data are needed to evaluate this approach. In the pilot study, we will measure BPA levels in urine samples provided by 90 WHI participants at baseline (SV1), year 1 (AV1) and year 3 (AV3) to address the following Specific Aims:
1. Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV. Human exposure to bisphenol A (BPA). Reprod Toxicol. Aug-Sep 2007;24(2):139-177.
2. Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environmental health perspectives. Apr 2005;113(4):391-395.
3. Dong S, Terasaka S, Kiyama R. Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells. Environ Pollut. Jan 2011;159(1):212-218.
4. Lee HR, Hwang KA, Park MA, Yi BR, Jeung EB, Choi KC. Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. Int J Mol Med. May 2012;29(5):883-890.
5. Miyakoshi T, Miyajima K, Takekoshi S, Osamura RY. The influence of endocrine disrupting chemicals on the proliferation of ERalpha knockdown-human breast cancer cell line MCF-7; new attempts by RNAi technology. Acta Histochem Cytochem. Apr 28 2009;42(2):23-28.
6. Pupo M, Pisano A, Lappano R, et al. Bisphenol A Induces Gene Expression Changes and Proliferative Effects through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts. Environ Health Perspect. Aug 2012;120(8):1177-1182.
7. Tilghman SL, Bratton MR, Segar HC, et al. Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS One. 2012;7(3):e32754.
8. Vivacqua A, Recchia AG, Fasanella G, et al. The food contaminants bisphenol A and 4-nonylphenol act as agonists for estrogen receptor alpha in MCF7 breast cancer cells. Endocrine. Dec 2003;22(3):275-284.
9. Weber Lozada K, Keri RA. Bisphenol A increases mammary cancer risk in two distinct mouse models of breast cancer. Biology of reproduction. Sep 2011;85(3):490-497.
10. Vokel W, Colnot T, Csanady GA, Filser JG, Dekant W. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem Res Toxicol. Oct 2002;15(10):1281-1287.
11. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environmental health perspectives. Jan 2008;116(1):39-44.
12. Volkel W, Kiranoglu M, Fromme H. Determination of free and total bisphenol A in human urine to assess daily uptake as a basis for a valid risk assessment. Toxicology letters. Jul 10 2008;179(3):155-162.
13. Weschler CJ. Changes in indoor pollutants since the 1950s. Atmos Environ. Jan 2009;43(1):153-169.
14. Kubwabo C, Kosarac I, Stewart B, Gauthier BR, Lalonde K, Lalonde PJ. Migration of bisphenol A from plastic baby bottles, baby bottle liners and reusable polycarbonate drinking bottles. Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment. Jun 2009;26(6):928-937.
15. Markham DA, Waechter JM, Wimber M, et al. Development of a Method for the Determination of Bisphenol A at Trace Concentrations in Human Blood and Urine and Elucidation of Factors Influencing Method Accuracy and Sensitivity. J Anal Toxicol. Jul-Aug 2010;34(6):293-303.
16. Waechter J, Thornton C, Markham D, Domoradzki J. Factors affecting the accuracy of bisphenol a and bisphenol a-monoglucuronide estimates in Mammalian tissues and urine samples. Toxicology mechanisms and methods. 2007;17(1):13-24.
17. Ye X, Bishop AM, Reidy JA, Needham LL, Calafat AM. Temporal stability of the conjugated species of bisphenol A, parabens, and other environmental phenols in human urine. Journal of exposure science & environmental epidemiology. Sep 2007;17(6):567-572.
18. Nepomnaschy PA, Baird DD, Weinberg CR, Hoppin JA, Longnecker MP, Wilcox AJ. Within-person variability in urinary bisphenol A concentrations: measurements from specimens after long-term frozen storage. Environ Res. Aug 2009;109(6):734-737.
19. Ye X, Wong LY, Bishop AM, Calafat AM. Variability of urinary concentrations of bisphenol A in spot samples, first morning voids, and 24-hour collections. Environmental health perspectives. Jul 2011;119(7):983-988.
20. Mahalingaiah S, Meeker JD, Pearson KR, et al. Temporal variability and predictors of urinary bisphenol a concentrations in men and women. Environmental health perspectives. Feb 2008;116(2):173-178.
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.