Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes

Evidence has shown that polymorphisms of various genes known to be involved in estrogen biosynthesis and function are associated with estrogen-dependent diseases (EDDs). These genes include CYP17A1, estrogen receptor 1 (ESR1), and 2 (ESR2). Phthalates are considered estrogenic endocrine disruptors, and recent research has suggested that they may act as a risk factor for EDDs. However, extremely few studies have assessed the effects of gene–environment interaction on these diseases. We recruited 44 patients with endometriosis or adenomyosis, 36 patients with leiomyoma, and 69 healthy controls from a medical center in Taiwan between 2005 and 2007. Urine samples were collected and analyzed for seven phthalate metabolites using liquid chromatography tandem mass spectrometry. Peripheral lymphocytes were used for DNA extraction to determine the genotype of CYP17A1, ESR1, and ESR2. Compared to controls, patients with leiomyoma had significantly higher levels of total urinary mono-ethylhexyl phthalate (ΣMEHP) (52.1 vs. 29.6 μg/g creatinine, p = 0.040), mono-n-butyl phthalate (MnBP) (75.4 vs. 51.3 μg/g creatinine, p = 0.019), and monoethyl phthalate (MEP) (103.7 vs. 59.3 μg/g creatinine, p = 0.031). In contrast, patients with endometriosis or adenomyosis showed a marginally increased level of urinary MEHP only. Subjects who were homozygous for both the ESR1 C allele (rs2234693) and CYP17A1 C allele (rs743572) showed a significantly increased risk for leiomyoma (OR = 19.8; 95 % CI, 1.70; 231.5; p = 0.017) relative to subjects with other genotypes of ESR1 and CYP17A1. These results were obtained after adjusting for age, cigarette smoking, MEHP level, GSTM1 genotype and other covariates. Our results suggested that both CYP17A1 and ESR1 polymorphisms may modulate the effects of phthalate exposure on the development of leiomyoma. Similar content being viewed by others

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DNA Cell Biol 28:633–636 Zhao Y, Zhang W, Wang S (2008) The expression of estrogen receptor isoforms alpha, beta and insulin-like growth factor-I in uterine leiomyoma. Gynecol Endocrinol 24:549–554 Acknowledgments We are also greatly indebted to the gynecologists of the Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, and to our colleagues, especially for Ms. H-Y Chen and Ms. P-J Lin, at the National Health Research Institute, Miaoli, Taiwan. These two groups assisted us with subject recruitment and sample collection. We also thank Ms. M-C Chung and Mr. J-H Lu for their technical assistance of genetic polymorphism. Funding sources We are grateful for financial support from the National Health Research Institute (grant nos.: EO-095-PP-09, EO-096-PP-09 and EH-102-PP-02) and National Science Council, Taiwan [grant number; NSC 102-2632-B-037-001-MY3]. Author information Authors and Affiliations Corresponding authors Additional information Responsible editor: Philippe Garrigues Electronic supplementary material Below is the link to the electronic supplementary material. ESM 1 (download DOC ) (DOC 68 kb) Rights and permissions About this article Cite this article Huang, PC., Li, WF., Liao, PC. et al. Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes. Environ Sci Pollut Res 21, 13964–13973 (2014). https://doi.org/10.1007/s11356-014-3260-6 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s11356-014-3260-6