PBDEs in Tissues of Women With and Without Breast Cancer

Institution: Public Health Institute
Investigator(s): Myrto  Petreas , Ph.D., M.P.H. -
Award Cycle: 2004 (Cycle 10) Grant #: 10IB-0061 Award: $67,779
Award Type: IDEA
Research Priorities
Etiology>Environment and gene/environment interactions: nature vs. nurture



Initial Award Abstract (2004)
Polybrominated diphenyl ethers (PBDEs) are a class of chemicals used as flame retardants in many commonly used consumer products, such as electronics and home furnishings. They persist in the environment and they accumulate into our fatty tissues. Levels of PBDEs are rising worldwide, and we recently discovered that California women have the highest levels in the world, probably because of the extensive use of PBDEs to meet the State's fire safety standards. PBDEs disrupt thyroid function and impair development in animal studies. There is no information yet on any connection between PBDEs and breast cancer, but the publicized high levels of PBDEs fuel the public's anxiety.

We propose to measure PBDEs in samples of breast fat collected from women with and without breast cancer. We will then test to see if, as a group, women with breast cancer have higher levels of PBDEs in their body fat than women without breast cancer. If that is true, then PBDEs may be considered a risk factor for the disease, after adjusting for other known risk factors.

We have already collected breast fat samples in the course of our earlier studies that investigated the presence of a number of environmental contaminants and breast cancer. We also have extensive questionnaires from these women on their health histories, occupation, demographics, diet and hobbies and activities that may involve exposures to chemical contaminants. We plan to analyze the samples in the lab and measure PBDEs. We will then explore associations between the measured levels of PBDEs and information from the questionnaires to see:
  1. whether women with breast cancer have higher levels of PBDEs than women without breast cancer, and
  2. what characteristics and/or behaviors are linked to increased levels of PBDEs in our bodies.
The innovative aspect of our proposal is the investigation of PBDEs as possible risk factors for breast cancer. PBDE levels are rising, and California women have the highest levels in the world. Although speculative, an exploration of the possible role of PBDEs is compelling.


Final Report (2007)
We accomplished our first objective, i.e., we established and validated an appropriate analytical method to ensure the highest quality of laboratory results. We optimized a new instrument for these analyses and we were able to detect and measure all the targeted contaminants in the same analytical run. This is very critical in preserving preciously small samples.

We accomplished our second objective, i.e. we analyzed breast adipose specimens for all major PBDE congeners. At the same time, major PCB congeners were also analyzed to allow for comparisons with other studies (congeners are variations or configurations of a common chemical compound; for example, polychlorinated biphenyls (PCBs) occur in 209 different forms, or congeners). A total of 152 valid measurements were performed. In agreement with information on levels and prevalence of PBDEs, we confirmed that PBDE concentrations in US populations are at least ten-fold higher than concentrations in European populations, consistent with the wider use of PBDEs in the US market.

We accomplished our third specific aim (link the PBDE results to our established data base of questionnaire information). Based on our preliminary analyses, no statistically significant differences were found between cases and controls for any of the chemicals examined. We also examined the relationship between dietary habits and disease outcome and found no statistically significant differences between cases and controls. Neither the reported residential proximity to potential sources of PBDEs and PCBs, nor occupational exposures differed among breast cancer cases and benign controls.

We accomplished our fourth specific aim (case-control analysis) by calculating age- and race-adjusted odds ratios and their 95% confidence intervals by conducting logistic regression analysis. Measurements for patients with DCIS were too few for inclusion in these age-adjusted models and they were excluded from the case-control analysis.

Because we did not find any statistically significant differences between breast cancer cases and benign controls, we pooled all three groups together (N=152) in order to explore our secondary aims. All PBDE congeners were highly correlated with each other, indicating uniform sources of PBDE exposures.

We plan to assess the effect of several parameters (recorded by questionnaires) on disease outcome after carefully controlling for selected variables.

Although our preliminary analysis did not indicate any association between the major PDBE congeners examined and disease outcome, the results are limited by the relatively small sample size (152 valid specimens were analyzed).

We plan to assess the effect of several parameters (recorded by questionnaire) on disease outcome after carefully controlling for selected variables. We also plan to evaluate which parameters (characteristics, habits, etc.) may result in elevated PBDE exposures, again after controlling for confounding variables.


Symposium Abstract (2007)
Background: Investigations on possible links between environmental exposures to chemicals and breast cancer have resulted in contradictory results, partly because the decreasing body burdens of the studied chemicals (dioxins, DDT, PCBs) limit statistical power. Not all environmental exposures to chemical contaminants are decreasing, however. Concentrations of the polybrominated diphenyl ethers (PBDEs) are increasing exponentially, and we recently reported on the extremely high body burdens in California women. PBDEs are used as flame retardants and are known endocrine disrupters and developmental toxicants. No links to breast cancer have been investigated, but the ubiquity of PBDEs fuels the publicís anxiety. Objective: The purpose of this study was to analyze breast adipose specimens for PBDEs, analyze questionnaire data, and conduct a case-control analysis to determine whether (after adjusting for other risk factors) PBDEs contribute to breast cancer. As a secondary objective we plan to investigate the determinants of PBDE exposures in our population. Methods: In the late 1990s, we collected breast adipose samples in the course of our earlier case-control study that investigated the presence of organochlorine contaminants and breast cancer (Petreas et al. 2004; Reynolds et al. 2005). We have extensive questionnaires from these women on their health histories, occupation, demographics, diet, hobbies and activities. We analyzed the specimens for PBDEs and explored statistical associations between the measured levels of PBDEs and information from the questionnaires to see: a) whether women with breast cancer have higher levels of PBDEs than women without breast cancer, and b) what variables are linked to increased body burdens of PBDEs Results: Preliminary results from 155 participants confirm our earlier findings that California women have the highest levels of PBDEs, almost a hundred times higher than those reported from Europe and Japan. The concentrations of the five major PBDE congeners are shown along with major PCB congeners. PBDE congeners were highly correlated with each other (correlation coefficients varied from 0.70 to 0.98, p<0.01), suggesting similar sources of exposure. Results from a case-control analysis and a multiple linear regression to identify determinants of body burdens will be presented. Table 1. Concentrations (ng/g lipid) of major PBDEs and PCBs in all participants (n=155).
 
PBDE-47
PBDE-99
PBDE-100
PBDE-153
PBDE-154
PCB-153
PCB-180
PCB-138
PCB-118
                   

mean

148
43.8
24.2
26.0
6.7
187
132
119
36.3
sd
507
94.8
71.5
65.3
18.3
454
329
276
49.1
med
23.2
12.2
4.8
7.4
1.1
105
71.4
62.0
23.2
min
4.3
1.3
0.8
0.8
0.0
17.0
22.4
19.5
2.7
max
3,141
470
442
371
95.0
3,168
2,344
1,904
326



Symposium Abstract (2010)

S. Hurley, D. Goldberg, P. Reynolds, D. Nelson (Cancer Prevention Insitute of California, Berkeley, CA 94704), M. Petreas (California Department of Toxic Substances Control, Berkeley, CA 94710).

Background: Polybrominated diphenyl ethers (PBDEs) are a class of over 200 organohalogenated compounds widely used as flame retardants in consumer products and building materials. Because they readily leach out of the products in which they are embedded, PBDEs have become pervasive environmental contaminants and human exposures are widespread.

Objective: The objective of this study was to evaluate the risk of breast cancer associated with measurements of PBDEs in the breast fat of women.

Methods: We conducted a hospital-based case control study among 78 women diagnosed with invasive breast cancer and 56 controls diagnosed with benign breast conditions who underwent surgical breast biopsy at two hospitals in the San Francisco Bay Area, CA.

Breast adipose tissue samples were collected at the time of biopsy and analyzed for five congeners of PBDEs (BDE-47, BDE-99, BDE-100, BDE-153, and BDE-154). Statistical models were used to estimate the risk of breast cancer, after taking into account age and race. Results: Average PBDE levels were high, consistent with previous reports of elevated levels among the California population. No statistically significant elevated risks of breast cancer were found for any of the congeners nor for the total PBDEs measured.

Conclusions: Our results provide no evidence of an association between PBDE adipose concentrations measured at the time of diagnosis and breast cancer risk. However, given the strong biologic rationale for the carcinogenic potential of PBDEs, coupled with widespread exposures, further study is warranted. Future studies would benefit from a larger sample size, a more representative control series, and/or a prospective design.