Exposure to common flame retardants may raise risk of PTC

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Some flame retardants used in many home products appear to be associated with the most common type of thyroid cancer, papillary thyroid cancer (PTC), according to a Duke University study presented at The Endocrine Society’s 99th annual meeting, ENDO 2017, in Orlando.

“Thyroid cancer is the fastest increasing cancer in the US, with most of the increase in new cases being papillary thyroid cancer,” said the study’s lead investigator, Dr Julie Ann Sosa, professor of surgery and medicine at Duke University School of Medicine in Durham, North Carolina. “Recent studies suggest that environmental factors may, in part, be responsible for this increase.”

Many animal studies have demonstrated that several classes of flame retardants act as endocrine-disrupting chemicals and interfere with thyroid homeostasis (function), partly because they share a similar chemical structure with thyroid hormones, Sosa said. Therefore, she and her colleagues turned their attention to these flame retardants to study a possible relationship with PTC.

“Our study results suggest that higher exposure to several flame retardants in the home environment may be associated with the diagnosis and severity of papillary thyroid cancer, potentially explaining some of the observed increase in the incidence of thyroid cancer,” Sosa said. “This study is novel in that we collected and analyzed individuals’ house dust as a measure of exposure to flame retardants.”

Levels of flame retardants in house dust significantly correlate with personal exposures, she explained. The researchers collected dust samples from the homes of 140 study subjects: 70 with PTC and 70 individuals without evidence of thyroid disease or cancer as control subjects. Controls were matched on important characteristics, including age, sex, race/ethnicity, body mass index, household income and education level. Because all participants had lived in their homes for an average of approximately 11 years, Sosa said the researchers could assess long-term average exposure to these environmental chemicals. They also collected participants’ blood samples to analyse biomarkers of exposure to several flame retardants in the class known as polybrominated diphenyl ethers (PBDEs).

Just as PTC affects more women than men, most study participants (79%) were women, and their average age was 48 years. The investigators reported that higher levels in house dust of two flame retardants were associated with an increased odds of the home resident having PTC. Those were decabromodiphenyl ether (BDE-209), the most heavily used PBDE, and to a lesser degree, tris(2-chloroethyl) phosphate (TCEP), an organophosphate flame retardant. Participants whose BDE-209 levels in their dust were high were more than two times as likely to have thyroid cancer than those individuals with low BDE-209 concentrations.

Participants with high levels of TCEP in their house dust were more than four times as likely to have larger, more aggressive tumors that extended beyond the thyroid, according to the study. In contrast, participants with the highest dust levels of BDE-209 were 14 times as likely to be a PTC patient that did not have a common gene mutation (BRAF V600E). This mutation has been linked to PTC that tends to behave more aggressively. “This difference,” Sosa said, “begs more interrogation.”

This study was sponsored by funding from Fred and Alice Stanback, the Duke Cancer Institute, and the Nicholas School of the Environment at Duke University.

Abstract
Background: Papillary thyroid cancer (PTC) is the fastest increasing cancer in the U.S., and data suggest environmental factors, in part, may be responsible. Exposure to flame retardant chemicals (FRs) also has increased over the same time frame; given their thyroid disrupting potential, concern has been raised about their role in the epidemic of PTC.
Objective: We have evaluated relationships between exposure to a broad range of commonly used FRs and PTC occurrence and severity.
Methods: In a case-control study, we have recruited 140 participants (70 PTC cases and 70 controls matched on age and gender). Participants provided blood samples in which we measured biomarkers of exposure to several polybrominated diphenyl ethers (PBDE) FRs. Because levels of FRs in household dust are strongly correlated with personal exposure, we visited participants’ homes and collected dust samples for the assessment of additional types of FRs. Participant demographic and clinical information was collected via questionnaire, and tumor histology data were abstracted from medical records.
Results: Reflecting known gender differences in PTC risk, our final study population was 78.6% female. Overall, participants averaged 48 years of age and cases and controls were similar with respect to race and ethnicity, household income, and health history. Our results suggest that higher levels of some FRs, particularly decabromodiphenyl ether (BDE-209) and tris(2-chloroethyl) phosphate (TCEP) in dust, are associated with increased odds of developing PTC. Those with dust BDE-209 concentrations above the median were 2.29 times as likely to have PTC [95% confidence interval (95% CI): 1.03, 5.08] compared to those with low BDE-209. Associations with PTC differed by the presence or absence of the BRAF V600E mutation and measures of tumor aggressiveness. For example, those with the highest levels of BDE-209 in the dust were 14.2 times as likely to have BRAF negative (95% CI: 1.63, 123) and less aggressive tumors (i.e. small tumors without extra-thyroidal extension). TCEP, in contrast, was more strongly associated with larger, more aggressive tumors. For example, participants with house dust TCEP levels above the median were 4.14 times likely to have PTC with extra-thyroidal extension (95% CI: 1.01, 16.98), but were not significantly more likely to have PTC without extra-thyroidal extension (OR=2.13; 95% CI: 0.89, 5.07).
Conclusions: Taken together, our results suggest exposure to several FRs may be associated with the occurrence and severity of PTC.

Authors
Julie Ann Sosa, Kate Hoffman, Amelia Lorenzo, Craig M Butt and Heather Stapleton

The Endocrine Society material
ENDO 2017 abstract


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