Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis.
BACKGROUND
Phthalates are known to have estrogenic effects in cell models and experimental animals. However, the evidence regarding the effects of phthalates on human reproduction is still limited. We conducted a case-control study to determine whether estrogen-dependent diseases are associated with phthalate exposure and how the glutathione S-transferase M1 (GSTM1; a major detoxification enzyme) genotype modulates the risk.


METHODS
We recruited subjects who underwent laparotomy and had pathologic confirmation of endometriosis (EN) (n = 28), adenomyosis (AD) (n = 16) and leiomyoma (LEI) (n = 36) from the Department of Obstetrics and Gynecology at a medical center in Taiwan between 2005 and 2007. Controls (n = 29) were patients without any of the three aforementioned gynecologic conditions. Urine samples were collected before surgery and analyzed for seven phthalate metabolites using liquid chromatography-tandem mass spectrometry. Peripheral lymphocytes were used for GSTM1 genotype determination.


RESULTS
Patients with LEIs had significantly higher levels of total urinary mono-ethylhexyl phthalate (SigmaMEHP; 52.1 versus 18.9 microg/g creatinine, P < 0.05) than the controls, whereas patients with EN had an increased level of urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, P < 0.05). Subjects with GSTM1 null genotype had significantly increased odds for AD relative to those with GSTM1 wild genotype [odds ratio (OR) = 5.30; 95% CI, 1.22-23.1], even after adjustment for age and phthalate exposure. Subjects who carried the GSTM1 null genotype and had a high urinary level of SigmaMEHP showed a significantly increased risk for AD (OR = 10.4; 95% CI, 1.26-85.0) and LEIs (OR = 5.93; 95% CI, 1.10-31.9) after adjustment for age, compared with those with GSTM1 wild-type and low urinary level of SigmaMEHP.


CONCLUSIONS
These results suggest that both GSTM1 null and phthalate exposure are associated with AD and LEI. Larger studies are warranted to investigate potential interaction between GSTM1 null and phthalate exposure in the etiology of estrogen-dependent gynecologic conditions.
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
Po-Chin
PC
Huang
Eing-Mei
EM
Tsai
Wan-Fen
WF
Li
Pao-Chi
PC
Liao
Meng-Chu
MC
Chung
Ya-Hui
YH
Wang
Shu-Li
SL
Wang
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004715:Endometriosis / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D004781:Environmental Exposure; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic; D007889:Leiomyoma / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D010795:Phthalic Acids / Q000493:pharmacokinetics / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics
D017931:DNA Primers; D005982:Glutathione Transferase; D010795:Phthalic Acids; C032279:phthalic acid