Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: a gene-environment interaction.

OBJECTIVE: To investigate the occurrence of a gene-environment interaction between glutathione transferase (GST) gene polymorphisms (GSTM1, GSTT1, GSTP1, and GSTA1) and serum polychlorinated biphenyls (PCBs) levels. This is suggested as possible risk factors for endometriosis, a multifactorial gynecological disease. DESIGN: Case-control study conducted from 2002 to 2005. SETTING: Policlinico Umberto I, "Sapienza" University of Rome and Italian National Institute for Health, Rome. PATIENT(S): Italian women (N = 343), with laparoscopic diagnosis and histologic confirmation of the presence (cases, N = 181) or the absence (controls, N = 162) of endometriosis. INTERVENTION(S): Genomic DNA extraction, multiplex polymerase chain reaction (PCR), and restriction fragment length polymorphism analysis. Determination of serum concentrations of selected PCBs by ion-trap mass spectrometry (subgroup, 63 cases and 63 controls). MAIN OUTCOME MEASURE(S): Endometriosis diagnosis by laparoscopy, GST genotypes, serum PCB levels. RESULT(S): The genotype distributions of GSTM1, GSTA1, and GSTP1 did not show any statistically significant difference between cases and controls. The GSTT1 null genotype was negatively associated with the disease. The GSTP1 wild-type genotype in the presence of medium-high blood levels of PCB153, total PCBs, or of high levels of PCB180 significantly increased the risk of endometriosis, suggesting a multiplicative interaction. CONCLUSION(S): The GSTs polymorphisms per se do not increase the risk of developing endometriosis. However, a gene-environment interaction was observed for GSTP1(Ile/Ile) and GSTM1 null genotypes, modulating the effect of PCB153, PCB180, and of total PCBs on disease risk.

Pain and ovarian endometrioma recurrence after laparoscopic treatment of endometriosis: a long-term prospective study.

OBJECTIVE: To identify prognostic factors for pain and endometrioma recurrence after complete laparoscopic excision of endometrioma(s). DESIGN: Prospective observational study. SETTING: Tertiary care university hospital. PATIENT(S): One-hundred sixty-six consecutive women affected by uni- or bilateral ovarian endometrioma(s). INTERVENTION(S): Laparoscopic conservative treatment of endometriosis. MAIN OUTCOME MEASURE(S): Patient demographic characteristics, surgical findings, and surgical results were prospectively recorded. Postoperative follow-ups were carried out every 3 months to identify pain and/or endometrioma recurrence for a minimum of 3 years. RESULT(S): Dysmenorrheal, dyspareunia, and chronic pelvic pain recurred in 14.5%, 6%, and 5.4% of women, respectively. Prior surgery for endometriosis, adhesion extension, and use of ovarian stimulation drugs (OSD) were unfavorable prognostic factors for pain symptoms. Ovarian endometrioma recurred in 9.6% of cases; negative factors were prior surgery for endometriosis, OSD, pelvic adhesions, and high American Society for Reproductive Medicine disease scores. Postoperative pregnancy showed a significant protective effect on pain and disease recurrences. CONCLUSION(S): Prior surgery, presence of adhesions, and ovulation drugs are negative prognostic factors. Pregnancy has a protective effect on disease and pain recurrence.

Endometriosis and organochlorinated environmental pollutants: a case-control study on Italian women of reproductive age.

BACKGROUND: Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. OBJECTIVE: We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. METHODS: We conducted a case-control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p'-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. RESULTS: We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61-8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60-8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01-11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41-8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25-14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. CONCLUSIONS: The results of this study show that an association exists between increased PCB and p,p'-DDE serum concentrations and the risk of endometriosis.

Serum concentrations of beta-hexachlorocyclohexane in groups of the Italian general population: a human biomonitoring study.

Because of its persistence and toxicological profile, beta-hexachlorocyclohexane (beta-HCH) has been proposed for inclusion in the Stockholm Convention on persistent organic pollutants (POPs). Although the use of technical HCH, which is the primary source of beta-HCH in the environment, has been banned in the EU in 1978 and progressively at a global level, beta-HCH is still detectable in the general environment worldwide. Human exposure mostly occurs via food and may be of concern in areas where illegal use and/or improper disposal of stockpiles occurred and locally grown food is consumed. Exposure of the Italian general population to beta-HCH has been poorly characterised. Lack of human biomonitoring data severely hinders the ability to interpret potential increases in exposure related to situations of environmental risk. We carried out a human biomonitoring study aimed to provide baseline information on background exposure of the Italian general population to this pollutant. For this purpose, we analysed 116 serum samples from groups of subjects of both sex from the general population residing in three Italian towns at different latitudes. Serum concentrations of beta-HCH resulted to be comprised between 1.64 and 300 ng/g fat, with a median value of 18.0 ng/g fat and a 90th percentile of 65.9 ng/g fat. The serum concentrations detected are in line with those detected in most Western European countries.

Increased levels of polychlorobiphenyls in Italian women with endometriosis.

Endometriosis has been hypothesised to be linked to persistent and toxic organochlorinated chemicals. Dioxins and dioxin-like compounds have in particular been associated with the disease, mainly on the basis of experimental studies. Data in women are conflicting. A case-control study on 80 Italian nulliparous women of reproductive age was carried out to assess whether there is a correlation between the presence of endometriosis and blood levels of polychlorobiphenyls (PCBs), a family of ubiquitary environmental pollutants which comprises congeners with dioxin-like activity. Higher levels of PCBs were found in women with endometriosis. A mean cumulative value of 410 ng g(-1), lipid base, was found in cases versus the value of 250 ng g(-1) observed in the control group (odds ratio for upper tertile 4.0, CI 95% 1.3-13; p = 0.0003). PCB increase involved both dioxin-like (PCBs 105, 118, 156, and 167) and non-dioxin-like congeners (PCBs 101, 138, 153, 170, 180).