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The interaction effects of FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon exposure on damage in exon 19 and 21 of EGFR gene in coke oven workers

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Abstract

Polycyclic aromatic hydrocarbon (PAH) exposure and genetic susceptibility were conductive to genotoxic effects including gene damage, which can increase mutational probability. We aimed to explore the dose-effect associations of PAH exposure with damage of exons of epidermal growth factor receptor (EGFR) and breast cancer susceptibility gene 1 (BRCA1), as well as their associations whether modified by Flap endonuclease 1 (FEN1) genotype. Two hundred eighty-eight coke oven male workers were recruited, and we detected the concentration of 1-hydroxypyrene (1-OH-pyr) as PAH exposure biomarker in urine and examined base modification in exons of EGFR and BRCA1 respectively, and genotyped FEN1 rs174538 polymorphism in plasma. We found that the damage indexes of exon 19 and 21 of EGFR (EGFR-19 and EGFR-21) were both significantly associated with increased urinary 1-OH-pyr (both Ptrend < 0.001). The levels of urinary 1-OH-pyr were both significantly associated with increased EGFR-19 and EGFR-21 in both smokers and nonsmokers (both P < 0.001). Additionally, we observed that the urinary 1-OH-pyr concentrations were linearly associated with both EGFR-19 and EGFR-21 only in rs174538 GA+AA genotype carriers (both P < 0.001). Moreover, FEN1rs rs174538 showed modifying effects on the associations of urinary 1-OH-pyr with EGFR-19 and EGFR-21 (both Pinteraction < 0.05). Our findings revealed the linear dose-effect association between exon damage of EGFR and PAH exposure and highlight differences in genetic contributions to exon damage and have the potential to identify at-risk subpopulations who are susceptible to adverse health effects induced by PAH exposure.

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Funding

This study was supported by the Natural Science Foundation of Guangdong Province (grant number 2018A030313606) and by the National Natural Science Foundation of China (grant numbers 81903381, 81803189, and 81860572), and Guangzhou Key Laboratory Fund (201905010004).

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  1. Siqin Chen and Yuefeng He contributed equally to this study.

Authors and Affiliations

  1. Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Innovation Center for Advanced Interdisciplinary Medicine, The Fifth Affiliated Hospital of Guangzhou Medical University, 621 Gangwan Rd, Guangzhou, 510700, Guangdong, China

    Siqin Chen, Qinghua He & Binyao Yang

  2. School of Public Health, Kunming Medical University, Kunming, Yunnan, China

    Yuefeng He & Jingwen Tan

  3. Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong, China

    Maosheng Yan

  4. School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong, China

    Yun Zhou

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  1. Siqin Chen
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Contributions

We thank all individuals who volunteered to participate in this study. M.Y., Q.H., J.T., Y.H., and S.C. collected the samples and established the database and conducted the experiments. M.Y, Y.Z., and Y.B. designed and carried out the study. S.C., Y.H., and B.Y. conducted the data analysis and drafted the manuscript. Y.B. revised the manuscript. All the authors had access to the data and reviewed and approved the final submitted manuscript.

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Correspondence to Binyao Yang.

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Chen, S., He, Y., Yan, M. et al. The interaction effects of FEN1 rs174538 polymorphism and polycyclic aromatic hydrocarbon exposure on damage in exon 19 and 21 of EGFR gene in coke oven workers. Environ Sci Pollut Res 28, 60692–60703 (2021). https://doi.org/10.1007/s11356-021-15013-y

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