Glutathione-S-transferase P1 gene polymorphism and susceptibility to endometriosis

D. Ertunc1,3, M. Aban1, E.C. Tok1, L. Tamer2, M. Arslan1 and S. Dilek1

1 Department of Obstetrics and Gynecology and 2 Department of Biochemistry, Mersin University, School of Medicine, 33079, Mersin, Turkey

3 To whom correspondence should be addressed. Email: devrimertunc{at}hotmail.com


    Abstract
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
BACKGROUND: Glutathione-S-tranferase (GST) is the part of the key phase II detoxifying enzyme system. Many studies have investigated the role of GSTM1 and GSTT1 gene polymorphisms in endometriosis. Although GSTP1 was found to be one of the most abundant types of GST in genital system, there are insufficient data about the importance of the role of GSTP1 gene polymorphism in endometriosis. METHODS: This case–control study involved 150 patients with endometriosis and 150 controls. The frequency of GSTP1 single nucleotide polymorphisms was evaluated using PCR and melting curve analysis. RESULTS: The proportion of GSTP1 ile/ile tended to be higher in patients with endometriosis than control group, although the difference was not significant [odds ratio (OR)=1.53; 95% confidence interval (CI)=0.95–2.46]. In contrast, GSTP1 val/val was significantly higher in control patients and seems protective for endometriosis (OR=0.10; 95% CI=0.02–0.42). CONCLUSION: The results of this study suggest that GSTP1 polymorphism might modulate the risk of endometriosis with significantly decreased risk for GSTP1 val/val and marginally increased risk for GSTP1 ile/ile. Further studies on not only the disease processes but also normal distribution of the enzyme in female genital tract may provide better understanding about the role of GST types and their polymorphs in endometriosis.

Key words: endometriosis/fluorophore/genital tract/glutathione-S-transferase P1/single nucleotide polymorphism


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity and is among the leading causes of hospitalization due to gynaecological problems (Eskenazi and Warner, 1997Go). Increasing evidence suggests that endometriosis is a polygenic and multifactorial disease, which indicates that multiple distinct pathways could be involved in its pathogenesis. The most popular hypothesis of pathogenesis is retrograde menstruation, which was introduced by Sampson (1940)Go. Because laparoscopy during menses has shown that up to 90% of women exhibit retrograde menstruation (Halme et al., 1984Go), the question why implantation rates of endometriotic plaques differ between women remains unclear. Several candidate genes have been investigated to specify the women at increased risk of endometriosis or to understand its pathogenesis (Campbell and Thomas, 2001Go).

In recent years, the role of polymorphisms in glutathione-S-transferase (GST) system as a risk factor for endometriosis has been sought thoroughly. GST are key phase II enzymes that catalyse the conjugation of glutathione to numerous potentially genotoxic compounds, including aliphatic aromatic heterocyclic radicals, epoxides and arene oxides (Autrup, 2000Go). Although not entirely consistent, several studies suggest that there is a correlation between endometriosis and GSTM1 or GSTT1 genotype (Baranov et al., 1996Go; Baranova et al., 1999Go; Hsieh et al., 2004Go; Hur et al., 2004Go).

GSTP1, located at 11q13, is involved in the detoxification of electrophilic compounds by glutathione conjugation, like other members in GST family (Autrup, 2000Go). Two genetic polymorphisms have been found in exon 5 and exon 6, both resulting in amino acid substitutions. However, only the transition in exon 5 was linked to enzymatic activity since this is located within the region coding for the active site of the enzyme. The genetic change in exon 5 results in polymorphism at codon 105, where an adenosine-to-guanidine (A->G) transition causes an Ile-to-Val substitution (Zimniak et al., 1994Go).

The cellular concentration and distribution of GST differ widely between tissues, and GST gene expression is differentially regulated by both endogenous and exogenous factors. Moreover, it has been demonstrated that different GST vary significantly in efficiency and enantio-selectivity for a number of toxic products (Hu et al., 1996aGo,b). In spite of the abundance of studies on GSTM1 and GSTT1 genotypes, and with respect to gaps in the current epidemiological knowledge base, there is insufficient data about the association of endometriosis with GSTP1 genotype. Furthermore, since GSTP1 is a key player in biotransformation and bioactivation of certain environmental pollutants (Harries et al., 1997Go), GSTP1 may be even more important than other GST in the pathogenesis of endometriosis. For this reason, we investigated GSTP1 genotype distribution in patients with endometriosis and controls.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Subjects
This case–control study was conducted between January 2004 and November 2004. Study subjects were recruited from consecutive 150 patients with surgically and histologically confirmed endometriosis in our university-based hospital. 108 patients were operated laparoscopically and 42 patients by laparotomy. These patients were operated for infertility work-up (29.3%), chronic pelvic pain (19.3%), tubal ligation (10.7%), ovarian cysts including endometriomas (26.0%), myoma uteri (13.3%) and reconstructive tubal surgery (1.3%). Control patients consisted of 150 regularly menstruating women without any lesion, suggesting endometriosis during comprehensive surgical exploration by the technique defined by Batt (1999)Go. This technique includes a thorough observation of appendix, small and large bowel, reproductive organs, peritoneum and diaphragm during surgery. These patients were operated for tubal ligation (43.3%), infertility work-up (8.7%), myoma uteri (23.3%) and ovarian cysts other than endometriomas (24.7%). Patients were not included in cases of drug treatment (oral contraceptives, GnRH agonists, progestins, danazol or letrozol) for endometriosis within 3 months prior to surgery, post-menopausal age, presence of intrauterine device, menstruation during surgery and normal or ectopic pregnancy. All patients gave written informed consent and the study protocol was approved by Ethical Committee of Mersin University.

All patients were interviewed by researchers who were unaware of the indications and types and findings of surgery. Researchers asked the patients to complete a questionnaire regarding general characteristics (age at surgery, height, weight, waist and hip circumference, educational level and socioeconomic status), lifestyle factors (smoking, alcohol intake), reproductive history and menstrual history (age at menarche, average duration of bleeding, average cycle length). Body mass index (BMI) was calculated as weight (kg) divided by the height2 (m2). Waist:hip ratio (WHR) was calculated by dividing waist by hip measurements. Staging of endometriosis was performed according to the revised American Society for Reproductive Medicine (1997)Go classification. The women in this study had similar ethnic background and none of the women was consuming regular alcohol. For this reason, we did not consider race and alcohol consumption in the statistical analyses.

PCR analysis for GSTP1 single nucleotide polymorphisms
Heparinized venous blood samples were collected from women in the study and control groups. Immediately after collection, whole samples were stored at +4°C until use. Genomic DNA was extracted from whole blood using High Pure PCR Template Preparation kits (Roche Diagnostics GmbH, Mannheim, Germany).

Appropriate fragment of GST P1 is amplified with specific primers from human genomic DNA which were synthesized according to Ko et al. (2000)Go. The amplicons are detected by fluorescence using specific pairs of hybridization probes which were synthesized by TIB MOLBIOL GmbH (Berlin, Germany). The hybridization probes consist of two different oligonucleotides that hybridize to an internal sequence of the amplified fragment during the annealing phase of PCR cycles. One probe is labelled at the 5'-end with a LightCycler-Red fluorophore (LightCycler-Red 640 or LightCycler-Red 705), and to avoid extension, modified at the 3'-end by phosphorylation. The other probe is labelled at the 3'-end with LightCycler-Fluorescein.

Only after hybridization to the template DNA do two probes come in close proximity, resulting in fluorescence resonance energy transfer (FRET) between two fluorophores. During FRET, LightCycler-Fluorescein, the donor fluorophore, is excited by the light source of the LightCycler Instrument, and part of the excitation energy is transferred to LightCycler-Red, the acceptor fluorophore. The emitted fluorescence of the LightCycler-Red fluorophore is measured by the LightCycler Instrument.

Genotype determination
The hybridization probes are also used to determine the genotype by performing a melting curve analysis after the amplification cycles are completed and the amplicons are formed. First, one oligonucleotide of each pair of hybridization probes hybridizes to a part of the target sequence. After that, the other oligonucleotide of each pair of hybridization probes spans the mutation site (mutation probe). The latter probe has a lower melting temperature (TM) than the anchor probe, thus ensuring that the fluorescent signal generated during the melting curve analysis is determined only by the mutation probe. The TM is dependent upon length and G + C content, but also upon the degree of homology between the mutation probe and the template DNA. If a mismatch between hybridization probe and target is present, the hybrid is destabilized, resulting in a lower TM. When the hybridization probe matches perfectly with the target, the hybrid has a higher TM.

Statistical analysis
Data were analysed by SPSS v10.0 (SPSS Inc., Chicago, IL, USA) for Windows. The characteristics of women in both groups were compared with Student's t-test or {chi}2-test. Genotype distributions were evaluated by {chi}2-test. Mantel–Haenszel analyses were used to estimate the odds ratios (OR) to test whether it was equal to one. Test for Hardy–Weinberg equilibrium was conducted by comparing observed versus expected genotype frequencies using a {chi}2-test. P ≤ 0.05 was considered statistically significant.


    Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
There were 103 patients (68.7%) who had stage I–II endometriosis and 47 patients (31.3%) who had stage III–IV endometriosis. The mean age of all endometriosis patients was 33.06±8.67 (range, 21–44), and the mean age of controls was 34.04±9.68 (range, 24–47); the difference was not statistically significant (P=0.36). The mean BMI, WHR and age at menarche were also comparable between controls and patients with endometriosis (P>0.05, Table I). The mean parity of control group was significantly higher than the mean parity of patients with endometriosis (P<0.001). There was a trend for an association of educational level with the presence of endometriosis (P=0.06, Table I). The patients with endometriosis had higher income than controls. The average cycle length and average duration of bleeding did not differ between the groups (P>0.05). Furthermore, American Fertility Society stage III–IV patients with endometriosis had significantly lower mean BMI and mean parity (P<0.05). These patients also tended to have longer average duration of bleeding, but the difference did not reach statistical significance (P=0.08, Table I).


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Table I. General characteristics of endometriosis patients and controls

 
Regarding both groups (controls and patients with endometriosis); the distribution of GSTP1 genotypes was in Hardy–Weinberg equilibrium. For statistical analyses, we used GSTP1 ile/val group as reference and calculated OR according to this group, since the distribution of this genotype was identical in both groups (Table II). Proportion of GSTP1 ile/ile in patients with endometriosis (52.0%) tended to be higher than control group (36.0%), but the difference was not significant (P=0.06) with adjusted OR of 1.79 (0.98–5.27). The percentage of individuals having GSTP1 val/val was significantly higher in controls than patients with endometriosis (14.7 versus 1.3%; adjusted OR=0.18; 95% CI=0.08–0.56; P=0.009). The distribution of GSTP1 ile/ile, ile/val and val/val were comparable between patients with stage I–II (52.5, 45.6 and 1.9% respectively) and with stage III–IV (51.1, 48.9 and 0% respectively; P=0.61).


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Table II. Glutathione-S-transferase P1 (GSTP1) genotype distribution among patients and controls

 

    Discussion
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Recent biochemical and epidemiological studies have led to the conclusion that polymorphic GST are important enzymes in the metabolism and inactivation of numerous known or suspected endogenous and exogenous compounds (Autrup, 2000Go). It is likely that there are multiple mechanisms by which endometriosis might occur (Donnez et al., 2002Go). There is an increasing awareness of potential links between reproductive health and environmental factors. Although inconsistent, epidemiological data suggest that there is an association between endometriosis and environmental factors including cigarette smoking, alcohol use, caffeine intake or exposure to environmental pollutants such as polycyclic aromatic hydrocarbons and dioxins (Seli et al., 2003Go). Based on the facts that allelic variants of GST have different ability to conjugate substances to glutathione, and that the increase of risk of endometriosis with certain GST polymorphisms, we hypothesized that GSTP1 variants may also modulate the risk of this disease.

The results of the present study indicate that polymorphic GSTP1 may play an important role in endometriosis. However, GSTP1 gene does not have a major effect on the stage of the disease. We found that GSTP1 val/val was associated with significantly decreased risk of endometriosis and seems to be protective. Although the difference was not significant, patients with GSTP1 ile/ile are at 1.5-fold higher risk of developing endometriosis. The molecular mechanisms by which the expressing genotypes of GSTP1 loci may be linked to the increased or decreased risk of endometriosis remain to be elucidated, but most probably through involvement of environmental toxins and/or its metabolites (Rier and Foster, 2002Go; Johnson et al., 1997Go; Yang et al., 1997Go).

In the first report about GST polymorphisms and endometriosis, it has been suggested that GSTM1-null polymorphism is associated with increased risk of endometriosis (Baranov et al., 1996Go). GSTM1-null polymorphism was found to be significantly higher in endometriosis patients in a French population with 77% having this polymorphism (Baranova et al., 1999Go). A tendency to endometriosis was also observed in GSTT1-negative subjects in the same study, but it did not reach statistical significance. These findings, however, were not supported by later studies (Hadfield et al., 2001Go; Hur et al., 2004Go). Furthermore, Hur et al. (2004)Go found no association between endometriosis and GSTP1 polymorphism in Korean women, in contrast to our findings.

The differential effect of GSTP1 genotypes on the endometriosis risk might result from enantio-selectivity of these genotypes. A large inter-individual variation in GSTP1 activity has been shown using 1-chloro-2,4-dinitrobenzene (Hu et al., 1996bGo). GSPT1 ile/ile was found 3-fold more effective than GSTP1 val/val in detoxification of this product. In contrast, GSTP1 val/val had a 7-fold higher efficiency for polycyclic aromatic hydrocarbons. Since an association between environmental pollutants and endometriosis has been shown (Rier et al., 1993Go; Johnson et al., 1997Go; Seli et al., 2003Go), it is probable that GSTP1 val/val might be involved in detoxification of endogenous or exogenous toxic substances related to endometriosis, and may decrease the risk of this disease by this mechanism. In contrast, GSTP1 ile/ile might inactivate other environmental or endogenous toxic substances that are not directly involved in the pathogenesis of endometriosis. Alternatively, although GST are generally recognized as detoxifying enzymes, they may also be involved in generation and activation of toxic compounds (Hayes and Pulford, 1995Go).

Interestingly, similar results have also been attained about GSTP1 variants in benign disease processes of other systems. Juronen et al. (2000)Go defined GSTP1 val/val as a genetic risk factor for the development of cortical cataract, whereas GSTP1 ile/ile was protective. In smokers, GSTP1 val/val genotype was found to be associated not only with an increased risk of decline of lung function, but also with the acceleration of this process (He et al., 2002Go).

Although GSTM1 and GSTT1 variants have been studied intensively, insufficient human data about the types and distribution of GST through genital system and peritoneum hinder our ability to draw exact conclusions on which type(s) of GST may be more important in possible pathogenesis of endometriosis. In the human ovary, GSTP isoenzymes were expressed at relatively high levels in stroma (Rahilly et al., 1991Go). The authors suggested that GSTP might be involved in proliferation and/or differentiation processes. Although only one study has looked for an association between ovarian carcinoma and GSTP genotype (Spurdle et al., 2001Go), the results of epidemiological data do not confirm an association between ovarian cancer and any polymorphic GST isoenzymes (Coughlin and Hall, 2002). However, GSTP isoenzyme was almost consistently found to be related to drug resistance in ovarian carcinomas in many studies (Hamada et al., 1994Go; Cheng et al., 1997Go; Kigawa et al., 1998Go; Ghalia et al., 2000Go), indicating an important role of this isoenzyme in the genital system.

In conclusion, we found that GSTP1 polymorphism might modulate the risk of endometriosis with significantly decreased risk for GSTP1 val/val and a trend for increased risk for GSTP1 ile/ile. The involvement and the significance of different GST in endometriosis are controversial. On the other hand, the central role of GST in detoxification of endogenous and exogenous compound have been well established. Regarding the importance of these compounds in the pathogenesis of endometriosis, the changes in expression of GST may modulate the risk of this disease. Further studies on not only the disease processes but also normal distributions in female genital tract may provide better understanding about the role of GST types and their polymorphs in endometriosis.


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
American Society for Reproductive Medicine (1997) Revised classification of endometriosis: 1996. Fertil Steril 67, 817–821.[CrossRef][ISI][Medline]

Autrup H (2000) Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response. Mutation Res 464, 65–76.[ISI][Medline]

Baranov VS, Ivaschenko T, Bakay B, Aseev M, Belotserkovskaya R, Baranova H, Malet P, Perriot J, Mouraire P, Baskakov VN et al. (1996) Proportion of the GSTM1 0/0 genotype in some Slavic populations and its correlation with cystic fibrosis and some multifactorial diseases. Hum Genet 97, 516–520.[CrossRef][ISI][Medline]

Baranova H, Canis M, Ivaschenko T, Albuisson E, Bothorishvilli R, Baranov V, Malet P and Bruhat MA (1999) Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis. Mol Hum Reprod 5, 636–641.[Abstract/Free Full Text]

Batt RE (1999) Abdominopelvic diagnostic laparoscopy. In Hunt R (ed.) Text and Atlas of Female Infertility Surgery, 3rd edn. St Louis, Mosby, pp. 372–385.

Campbell IG and Thomas EJ (2001) Endometriosis: candidate genes. Hum Reprod Update 7, 15–20.[Abstract/Free Full Text]

Cheng X, Kigawa J, Minagawa Y, Kanamori Y, Itamochi H, Okada M and Terakawa N (1997) Glutathione S-transferase-pi expression and glutathione concentration in ovarian carcinoma before and after chemotherapy. Cancer 79, 521–527.[CrossRef][ISI][Medline]

Coughlin SS and Ingrid IJ (2002) Glutathione S-transferase polymorphisms and risk of ovarian cancer: A HUGE review. Genet Med 4, 250–257.[ISI][Medline]

Donnez J, Van Langendonckt A, Casanas-Roux F, Van Gossum JP, Pirard C, Jadoul P, Squifflet J and Smets M (2002) Current thinking on the pathogenesis of endometriosis. Gynecol Obstet Invest 54 (Suppl 1), 52–58.[CrossRef][ISI][Medline]

Eskenazi B and Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin North Am 24, 235–258.[ISI][Medline]

Ghalia AA, Rabboh NA, el Shalakani A, Seada L and Khalifa A (2000) Estimation of glutathione S-transferase and its Pi isoenzyme in tumor tissues and sera of patients with ovarian cancer. Anticancer Res 20, 1229–1235.[ISI][Medline]

Hadfield RM, Manek S, Weeks DE, Mardon HJ, Barlow DH and Kennedy SH; OXEGENE Collaborative Group, (2001) Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1. Mol Hum Reprod 7, 1073–1078.[Abstract/Free Full Text]

Halme J, Hammond MG, Hulka JF, Raj SG and Talbert LM (1984) Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol 64, 151–154.[Abstract]

Hamada S, Kamada M, Furumoto H, Hirao T and Aono T (1994) Expression of glutathione S-transferase-pi in human ovarian cancer as an indicator of resistance to chemotherapy. Gynecol Oncol 52, 313–319.[CrossRef][ISI][Medline]

Harries L, Stubbins MJ, Forman D, Howard GC and Wolf CR (1997) Identification of genetic polymorphisms at the glutathione S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 18, 641–644.[Abstract]

Hayes JD and Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 30, 445–600.[Abstract]

He JQ, Ruan J, Connett JE, Anthonisen NR, Pare PD and Sandford AJ (2002) Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers. Am J Respir Crit Care Med 166, 323–328.[Abstract/Free Full Text]

Hsieh YY, Chang CC, Tsai FJ, Lin CC, Chen JM and Tsai CH (2004) Glutathione S-transferase M1*null genotype but not myeloperoxidase promoter G-463A polymorphism is associated with higher susceptibility to endometriosis. Mol Hum Reprod 10, 713–717.[Abstract/Free Full Text]

Hu X, Benson PJ, Srivastava SK, Mack LM, Xia H, Gupta V, Zaren HA and Singh SV (1996a) Glutathione S-transferases of female A/J mouse liver and forestomach and their different induction by anticarcinogenic organosulfides from garlic. Arch Biochem Biophys 336, 199–214.[CrossRef][ISI][Medline]

Hu X, Srivastava SK, Xia H, Awasthi YC and Singh SV (1996b) An alpha class mouse glutathione S-transferase with exceptional catalytic efficiency in the conjugation of glutathione with 7b,8a-dihydroxy-9a,10a-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene. J Biol Chem 271, 32684–32688.[Abstract/Free Full Text]

Hur SE, Lee JY, Moon HS and Chung HW (2004) Polymorphisms of the genes encoding the GSTM1, GSTT1 and GSTP1 in Korean women: no association with endometriosis. Mol Hum Reprod 11, 15–19.[CrossRef][ISI][Medline]

Johnson KL, Cummings AM and Birnbaum LS (1997) Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls. Environ Health Perspect 105, 750–755.[ISI][Medline]

Juronen E, Tasa G, Veromann S, Parts L, Tiidla A, Pulges R, Panov A, Soovere L, Koka K and Mikelsaar AV (2000) Polymorphic glutathione S-transferases as genetic risk factors for senile cortical cataract in Estonians. Invest Ophthalmol Vis Sci 41, 2262–2267.[Abstract/Free Full Text]

Kigawa J, Minagawa Y, Kanamori Y, Itamochi H, Cheng X, Okada M, Oishi T and Terakawa N (1998) Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer. Cancer 82, 697–702.[CrossRef][ISI][Medline]

Ko Y, Koch B, Harth V, Sachinidis A, Thier R, Vetter H, Bolt HM and Bruning T (2000) Rapid analysis of GSTM1, GSTT1 and GSTP1 polymorphisms using real-time polymerase chain reaction. Pharmacogenetics 10, 271–274.[CrossRef][ISI][Medline]

Rahilly M, Carder PJ, al Nafussi A and Harrison DJ (1991) Distribution of glutathione S-transferase isoenzymes in human ovary. J Reprod Fertil 93, 303–311.[ISI][Medline]

Rier S and Foster WG (2002) Environmental dioxins and endometriosis. Toxicol Sci 70, 161–170.[Abstract/Free Full Text]

Rier SE, Martin DC, Bowman RE, Dmowski WP and Becker JL (1993) Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundam Appl Toxicol 21, 433–441.[CrossRef][ISI][Medline]

Sampson JA (1940) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14, 422–469.

Seli E, Berkkanoglu M and Arici A (2003) Pathogenesis of endometriosis. Obstet Gynecol Clin N Am 30, 41–61.[CrossRef][Medline]

Spurdle AB, Webb PM, Purdie DM, Chen X, Green A and Chenevix-Trench G (2001) Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype. Carcinogenesis 22, 67–72.[Abstract/Free Full Text]

Yang JZ, Yagminas A and Foster WG (1997) Stimulating effects of 4-chlorodiphenyl ether on surgically induced endometriosis in the mouse. Reprod Toxicol 11, 69–75.[CrossRef][ISI][Medline]

Zimniak P, Nanduri B, Pikula S, Bandorowicz-Pikula J, Singhal SS, Srivastava SK, Awasthi S and Awasthi YC (1994) Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem 224, 893–899.[Abstract]

Submitted on January 14, 2005; resubmitted on April 4, 2005; accepted on April 7, 2005.





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