Persistent Organic Pollutants & Breast Cancer Risk

Institution: Cancer Prevention Institute of California
Investigator(s): Peggy Reynolds, Ph.D. - Peggy Reynolds, Ph.D. -
Award Cycle: 2010 (Cycle 16) Grant #: 16ZB-8501A Award: $2,917,791
Award Type: SRI Program Directed Awards
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle

This is a collaboration with: 16ZB-8501 -

Final Report (2018)

Persistent organic pollutants (POPs) are a large and diverse group of pervasive environmental contaminants of concern for breast cancer risk due to their toxic properties and ability to disrupt the endocrine system. The primary objective of this study was to investigate the risk of breast cancer associated with body burden levels of POPs among participants in the California Teachers Study (CTS). Originally this project was designed to focus on four broad classes of POPs compounds including: polybrominated diphenyl ethers (PBDEs) and other newer replacement brominated flame retardants (BFRs); organochlorine pesticides (OCPs); and polychlorinated biphenyls (PCBs). However, because our initial results indicated limited measurability of the newer replaement BFRs in blood, we replaced these compounds with perfluoroalkyl and polyfluoroalkyl substances (PFASs). Our project had three specific aims: (1.) describe disparities in, and predictors of, blood levels of PBDEs in a subset of 360 CTS members with no history of breast cancer; (2.) estimate the risk of breast cancer associated with body burden levels of POPs among the full CTS cohort; (3.) use questionnaire data and record linkage to birth files for a subset of the CTS to enhance exposure estimates for two potential windows of susceptability including the perinatal and early reproductive years.

To address Aim#1, we conducted a number of analyses among cancer-free controls, including geographic-based analyses that identified previously unrecognized sources of exposure – residential proximity to solid waste sites and drinking water contamination – as potentially important routes of exposure to PBDEs and PFASs, respectively. Temporal analyses of PBDE and PFAS levels indicated mixed success of regulatory and voluntary actions to reduce human exposures. Furthermore, these analyses highlighted disparites in exposure and rates of change in body burden levels associated with age, suggesting comparative differences in the relative importance of different exposures routes by age and/or possible age-related differences in the metabolisim and excretion of these compounds.

Overall our risk analyses for Aim#2 did not provide evidence of a relationship between any of the POPs and breast cancer risk. However, for certain selected subsets of study participants, there was some suggestion of both increased and decreased risks for some of the individual POPs compounds. While based on small numbers of cases and generally not statistically significant, the findings from these subset analyses might suggest that the effects of exposure are limited to specific subtypes of breast cancer, may vary by host factors related to endogenous hormone levels, and may exert either protective effects or increased risks. Conversely, they may be chance findings or artifacts of study design. Of primary concern is the possibility of reverse causation due to the fact that the blood specimens were collected after treatment and on average 35 months after diagnosis among the cases.

To address Aim#3, we conducted a preliminary evaluation of whether the risk of breast cancer was elevated among parous women who lived in close proximity to a solid waste facility that may have been a source of PBDE exposure at the time they were pregnant with their first child – a window of potential susceptibility. While these analyses showed no association, they were hindered by missing data on facility type and dates of operation that ultimately precluded our ability to continue to pursue them beyond this preliminary exploration.

In the future we hope to identify and apply for additional sources of funding to continue to explore breast cancer and other health effects associated with POPs in this cohort of women as well as in other study populations. Especially important considerations in future research would be to better understand how serum POPs levels may be influenced by the onset or sequelae of disease and by specific treatment protocols. Additionally, we hope to be able to explore the degree to which genetic factors and other host characteristics might influence the endogenous hormonal milieu in a way that impacts the potential risk associated with exposures to these compounds.

Conference Abstract (2016)

Association between Serum PBDE Levels and Residential Proximity to Solid Waste Facilities/Landfills or Toxics Release Facilities

Ruiling Liu1, David O. Nelson1, Susan Hurley1, Myrto Petreas2, Yunzhu Wang2, Tan Guo2, June-Soo Park2, Pamela Horn-Ross1, Leslie Bernstein3, Hoda Anton-Culver4, Andrew Hertz1, Peggy Reynolds1,5
1Cancer Prevention Institute of California; 2 California Department of Toxic Substances Control; 3Beckman Research Institute of the City of Hope, Department of Population Sciences; 4University of California Irvine, School of Medicine; 5Stanford University School of Medicine, Department of Health Research and Policy

Polybrominated diphenyl ethers (PBDEs), chemicals commonly used as flame retardants, have been the source of some concern for a variety of health outcomes including breast cancer. Some studies have examined the relationship between characteristics of indoor environments and human PBDE body burden, but relatively few have considered the role of outdoor environments as potential exposure sources. We examined the association between serum PBDE levels in California women and residential proximity to solid waste facilities/landfills or toxics release facilities, which may release PBDEs into the environment. 481 participants (median age=66 years; range 40-94 years) from the California Teachers Study provided blood samples in 2011-2013, which were assayed for 19 PBDE congeners via Gas Chromatography/High Resolution Mass Spectrometry DFS. Information on solid waste facilities/landfills was obtained from the California Solid Waste Information System, and for toxics release facilities from the U.S. Environmental Protection Agency Toxics Release Inventory program. Facilities with potential for release of flame-retardants were identified and geocoded, and the distance to each participant’s residential address at time of blood draw was computed. Linear regression was used to examine the association between the proximity to those facilities and the serum levels of three most common PBDE congeners (BDE-47, -100 and -153), adjusting for age, race, body mass index and neighborhood (block group) socioeconomic status. Serum PBDE levels were lipid adjusted (ng/g lipid) and log-transformed for analysis. Subjects living within 10km (n=452) from any solid waste facility/landfill had approximately 45% higher serum BDE-47 levels than those living beyond 10km (p=0.04). Dose response was evident for residences within 3-9 km. Similar associations were not observed for BDE-100 or 153, or for proximity to toxics release facilities. Living within 10km of some solid waste facilities/landfills may be related to higher serum BDE-47 levels. More studies are needed to examine potential exposure routes. Acknowledgements: Funded by CBCRP grant #16ZB-8501.

Conference Abstract (2016)

Comparison of GC-HRMS and GC-MS/MS Methods for the Determination of Persistent Organic Pollutants in Human Serum

S.M.Crispo Smith1; Y Wang2; W Guo2; M. Petreas2; D. Nelson3; P. Reynolds3,4; R. Liu3; S. Hurley3; J-S. Park2
1Sequoia Foundation, La Jolla, CA
2California Department of Toxic Substance Control, Berkeley, CA
3Cancer Prevention Institute of California, Fremont, CA
4Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA

Serum analysis of persistent organic pollutants including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), are routinely performed for California Biomonitoring studies, such as the California Teacher’s Study. The California Teacher’s Study measures levels of persistent organic pollutants in California teachers and administrators serum samples collected from 2011 to present, in an effort to establish links between breast cancer and pollutants. Serum samples are extracted using an automated solid-phase extraction system. The sample extracts required separate injections for PCBs/OCPs and PBDEs on two different columns (a 60m SGE HT8-PCB and a 15m Agilent DB-5ms, respectively) installed on gas chromatograph/high resolution mass spectrometer (GC–HRMS, ThermoFisher, Bremen, Germany). A method for the simultaneous determination of 15 PCBs (-66,-74,-99,-101,-105,-118,-138,-153,-156,-170 -180,-183,-187,-194,-203), 7 OCPs (hexachlorobenzene, b-hexachlorocyclohexane, o,p’-DDT, p,p’-DDT, p,p’-DDE, oxychlordane, and trans-nonachlor), and 5 PBDEs (-47,-99,-100,-153,-154) was developed using gas chromatography/triple-quadrupole tandem mass spectrometry (GC-MS/MS, Agilent, Santa Clara, CA) equipped with a 30m DB-5ms column (Agilent). The method was confirmed using samples from the Arctic Monitoring and Assessment Program. The ease of use, 24 minute run time, and low cost of maintenance made this new method attractive for the projects requiring high throughput, like California Biomonitoring projects. Serum data (n=47 for PCB/OCP and n=297 for BDE) produced from GC-HRMS and GC-MS/MS analysis were compared to determine feasibility of using the GC-MS/MS method as an alternative for these large studies. Sample concentrations were determined using average response factors for the GC-HRMS method while calibration curve interpolation was used for the GC-MS/MS method. Most compounds of interest showed linear relationships in the results between the GC-HRMS and GC-MS/MS with slopes of 1.0 ± 0.2 and Pearson’s r values > 0.9, indicating both methods to be generally comparable. However, BDE-47 by the GC-MS/MS method was underestimated by 25%, particularly at high concentrations. The cause of this discrepancy is under investigation. Meanwhile, the issue with BDE-47 was resolved by calculating concentrations using average response factors for the GC-MS/MS method. Our new method improves our throughput and will provide benefits to large cohort studies in the California Biomonitoring Program.

Disclaimer: The views expressed herein are those of the authors and do not necessarily reflect those of the California Department of Toxic Substances Control.

Time Trends in Per- and Polyfluoroalkyl Substances (PFASs) in California Women: Declining Serum Levels, 2011-2015
Periodical:Environmental Science and Technology
Index Medicus: Environ Sci Technol.
Authors: Hurley S, Goldberg D, Wang M, Park J-S, Petreas M, Bernstein L, Anton-Culver H, Nelson DO
Yr: 2018 Vol: 52 Nbr: Abs: Pg:277-87