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. 2024 Aug;15(24):1805-1814.
doi: 10.1111/1759-7714.15411. Epub 2024 Jul 24.

Association between exposure to organophosphate flame retardants and epidermal growth factor receptor expression in lung cancer patients

Po-Ju Chen  1   2 , Po-Chen Lai  3 , Yueh-Chien Lu  1   2 , Bo-Lin Pan  1   2 , Wan-Ting Huang  4 , Chia-Te Kung  5 , Jui-Chin Chiang  1   2 , Fu-Jen Cheng  5 , Liang-Jen Wang  6 , Shau-Hsuan Li  7 , Wen-Chin Lee  8 , Yu-Che Ou  9 , Chin-Chou Wang  1   10   11   12   13
Affiliations

Association between exposure to organophosphate flame retardants and epidermal growth factor receptor expression in lung cancer patients

Po-Ju Chen et al. Thorac Cancer. 2024 Aug.

Abstract

Background: Organophosphate flame retardants (OPFRs) are extensively distributed in our environment, prompting concerns about potential health hazards, including lung injuries resulting from OPFR exposure.

Methods: The present study recruited 125 lung cancer patients, assessing their exposure to 10 OPFR compounds through urine samples. The final analysis comprised 108 participants after excluding those lacking epidermal growth factor receptor (EGFR) status and those with chronic kidney disease. Demographic and clinical characteristics, as well as urinary OPFR concentrations, were compared based on OPFR detection. Spearman correlation was conducted to explore the relationship between OPFR compounds, while logistic regression was used to identify OPFR compounds associated with EGFR mutation.

Results: The study revealed widespread OPFR exposure among lung cancer patients, with an overall detection frequency of 99.07%. Tris(2-butoxyethyl) phosphate (TBEP) exhibited a strong correlation to its metabolite bis(2-butoxyethyl) phosphate (r = 0.88, p < 0.01). Patients with TBEP in their urine had higher percentage of wild-type EGFR and the detection of TBEP was associated with a reduced likelihood of mutant EGFR expression.

Conclusions: OPFR exposure was prevalent in lung cancer patients, with TBEP detection identified as a factor with lower EGFR mutation expression. This study contributes to the understanding of OPFR exposure in lung cancer patients and underscores the significance of TBEP in evaluating EGFR mutation in this population.

Keywords: epidermal growth factor receptor; flame retardants; lung neoplasms.

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Conflict of interest statement

The authors assert that the research was carried out without the presence of any commercial or financial affiliations that might be interpreted as potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram illustrating participant selection. EFGR, epidermal growth factor receptor.
FIGURE 2
FIGURE 2
Detection frequencies of urinary OPFRs in lung cancer patients (n = 108). BBOEP, bis(2‐butoxyethyl) phosphate; BCEP, bis(2‐chloroethyl) phosphate; BDCPP, bis(1,3‐dichloro‐2‐propyl) phosphate; DnBP, di‐n‐butyl phosphate; DPHP, diphenyl phosphate; TBEP, tris(2‐butoxyethyl) phosphate; TCEP, tris(2‐chloroethyl) phosphate; TDCPP, tris(1,3‐dichloro‐2‐propyl) phosphate; TnBP, tri‐n‐butyl phosphate; TPHP, triphenyl phosphate; OPFR, organophosphate flame retardant.
FIGURE 3
FIGURE 3
Spearman correlations of urinary concentration of organophosphate flame retardants with a detection frequency of ≥50% in lung cancer patients. *p < 0.05, **p < 0.01. BBOEP, bis(2‐butoxyethyl) phosphate; DPHP, diphenyl phosphate; TBEP, tris(2‐butoxyethyl) phosphate; TnBP, tri‐n‐butyl phosphate.
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