Comparing the survival rates of patients with stage IIIC endometrial cancer undergoing sandwich therapy to those undergoing sequential chemotherapy and radiotherapy: a meta-analysis.

BACKGROUND: The use of additional treatment after surgery for stage IIIC endometrial cancer (EC) according to the Federation of Gynecology and Obstetrics (FIGO) is still a topic of discussion. This meta-analysis examined the effects of sandwich treatment and sequential treatment on the survival of individuals diagnosed with stage IIIC EC. METHODS: We examined the literature from various databases regarding the overall survival (OS) and adverse effects of the two additional therapies following surgery in individuals diagnosed with stage IIIC EC. Revman 5.4.1 was utilized to combine hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) for OS and toxicities. RESULTS: The findings comprised of five retrospective investigations involving a combined total of 800 individuals. The patients who underwent sandwich treatment did not demonstrate a notable improvement in survival rates over a period of 3 years. Upon eliminating the impact of extensive samples, it was discovered that sandwich therapy exhibited a superior 5-year overall survival compared to patients receiving sequential therapy. The effectiveness of sandwich therapy was superior to sequential therapy in terms of a 3-year OS for non-endometrioid histology, although the outcome did not reach statistical significance. The toxicities of both treatments were similar. CONCLUSIONS: In terms of long-term survival, sandwich therapy was found to be more advantageous than sequential therapy for patients with stage IIIC EC, with no significant disparity observed in the 3-year OS and toxicities between the two treatments. Sandwich therapy exhibited a tendency towards improved effectiveness in patients with histology other than endometrioid.

A case report of laparoscopic surgery for Mayer-Rokitansky-Küster-Hauser syndrome with preservation of functional primordial uterus.

BACKGROUND: In the past, the primary treatment for MRKH syndrome (Mayer-Rokitansky-Küster-Hauser syndrome) with a functional primordial uterus was surgical removal of the functional primordial uterus. In rare instances, the endometrium of the functional primordial uterus is well developed, and surgical preservation of the functional primordial uterus provides the possibility of preserving reproductive function for these patients. CASE PRESENTATION: A 14-year-old female was diagnosed with type I MRKH syndrome with a functional primordial uterus through physical examination and imaging investigations. We freed the functional primordial uterus through laparoscopic surgery and excised a portion of the lower myometrium to create an outlet at a lower uterine segment, which we then intermittently anastomosed to the tip of the artificial vagina. The patient recovered well after the surgery, and a re-examination showed no significant abnormalities. CONCLUSION: We were successful in preserving the functional primordial uterus using laparoscopic surgery in a patient with MRKH syndrome and connecting it to an artificial vagina through reconstructive surgery to ensure unobstructed menstrual drainage and preserve the reproductive potential of the patient.

Efficacy of lymph node dissection on stage IIICr of cervical cancer before CCRT: study protocol for a phase III, randomized controlled clinical trial (CQGOG0103).

BACKGROUND: Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer. METHODS: Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m²] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04555226.

Circ 003390/Eukaryotic translation initiation factor 4A3 promoted cell migration and proliferation in endometrial cancer via vascular endothelial growth factor signaling by miR-195-5p.

The differential expression of circRNA in different biological samples renders it as an ideal biomarker for disease diagnosis and identification of tissue development. In addition, the gradual clarification of the mode of action of circRNA in disease makes it as a potential therapeutic target. The purpose of this study is to investigate the role and regulating mechanism of circular RNA has circ 003390 (circWEE1) on Endometrial cancer (EC) genesis. To estimate clinical values of circWEE1 on cell migration and proliferation in EC, and its possible mechanisms. The expression of circWEE1 and EIF4A3in EC cells have been evaluated using qPCR and Western blot. The expression of circWEE1 and EIF4A3 levels were increased in patients with EC. Over-expression of circWEE1 or down-regulation of miR-195-5p promoted cell migration and proliferation in EC. Next, we verified that eIF4A3 binds to the circWEE1 mRNA transcript, circWEE1 served as a sponge that directly targeted miR-195-5p. Bioinformatics prediction forecast that miR-195-5p directly targeted VEGF at 3'-UTR, which was confirmed by luciferase reporter assay. Our findings indicate that Circular RNA hsa circWEE1/EIF4A3 promoted cell migration and proliferation in EC via VEGF signaling by miR-195-5p, which could provide pivotal potential therapeutic targets for the treatment of EC.

Interferon­stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response.

Endometrial carcinoma (EC) is one of the most common gynecological cancers with a poor prognosis. Therefore, clarifying the details of the molecular mechanisms is of great importance for EC diagnosis and clinical management. Interferon­stimulated gene 15 (ISG15) plays an important role in the development of various cancers. However, its role in EC remains unclear. High ISG15 expression was observed in EC, which was associated with poor clinical outcomes and pathological stage of patients with EC, thus representing a promising marker for EC progression. Further exploratory analysis revealed that the elevated ISG15 levels in EC were driven by aberrant DNA methylation, independent of copy number variation and specific transcription factor aberrations. Accordingly, knockdown of ISG15 by small interfering RNA attenuated the malignant cellular phenotype of EC cell lines, including proliferation and colony formation in vitro. Finally, investigation of the molecular mechanisms indicated that ISG15 promoted the cell cycle G1/S transition in EC. Furthermore, ISG15 promoted EC progression by activating the MYC proto­oncogene protein signaling pathway. Moreover, ECs with high levels of ISG15 harbored a more vital immune escape ability, evidenced not only by significantly less invasive CD8+ T cells, but also higher expression of T cell inhibitory factors, such as programmed death­ligand 1. These results suggest a tumor­promoting role of ISG15 in EC, which may be a promising marker for diagnosis, prognosis and therapeutic immunity.

Comparison of two laparoscopic vaginoplasties using a single peritoneal flap in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: To compare two laparoscopic vaginoplasties using a single peritoneal flap (SPF), namely the Hebei I technique and the Hebei II technique, for creation of a neovagina in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. METHODS: A comparative retrospective study was conducted at a university-based tertiary care hospital. From September 2008 to September 2019, 72 patients with MRKH syndrome underwent either the Hebei I technique (n = 49) or the Hebei II technique (n = 23). The perioperative results, complications and anatomical outcomes of two groups were recorded and compared. The functional results of patients who became sexually active were assessed through the Female Sexual Function Index (FSFI) questionnaire. RESULTS: Two techniques achieved anatomical and functional success without intraoperative complications. There was no significant difference in perioperative results, anatomical findings and the FSFI scores between the two groups. Patients in the Hebei II group had a relatively shorter operative time than those in the Hebei I group (P = 0.064). What is more, compared with the Hebei I group, the Hebei II group had significantly fewer granulomatous polyps at the top of the neovagina (P = 0.029) and less mucous production of the neovagina (P = 0.025) during the first 3 months after surgery. CONCLUSIONS: Both the Hebei I and Hebei II techniques are feasible approaches for creating a neovagina which can bring satisfactory anatomical and sexual outcomes in patients with MRKH syndrome. However, the Hebei II technique may be a good alternative to the Hebei I technique because of its relatively shorter operative time, fewer neovaginal secretions and fewer granulomatous polyps.

LncRNA PSMA3-AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.

The crucial roles of the long noncoding RNAs (lncRNAs) in the development of ovarian cancer (OC) have been extensively studied. According to the prediction result from the Kaplan-Meier Plotter database, high expression of lncRNA proteasome subunit α type-3 antisense RNA1 (PSMA3-AS1) is associated with the poor prognosis in patients with OC. Thus, the study aimed to investigate the role of lncRNA PSMA3-AS1 in OC. Reverse transcription quantitative polymerase chain reaction analysis revealed that PSMA3-AS1 expression was significantly upregulated in OC cells and tissues. PSMA3-AS1 silencing inhibited OC cell proliferation, migration, and invasion, as shown by results of cell counting kit-8, colony formation, wound healing, and Transwell assays, respectively. Additionally, PSMA3-AS1 deficiency suppressed tumor growth in vivo. Mechanistically, luciferase reporter and RNA pulldown assays implied that PSMA3-AS1 served as a competing endogenous RNA for miR-378a-3p to upregulate the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). GALNT3 was a target gene of miR-378a-3p in OC. Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.

CARLo-5 as an oncogenic gene in endometrial carcinoma.

The long noncoding RNA CARLo-5 is dysregulated in multiple types of human cancers. High CARLo-5 is a promising predictive factor for various cancers, including endometrial carcinoma (EC). Our previous study showed that the expression level of CARLo-5 was associated with advanced FIGO stage (The International Federation of Gynecology and Obstetrics), lymph node metastasis, and the poor survival of patients with EC. In the present study, we demonstrated that the downregulation of CARLo-5 could affect the proliferation, cell cycle, migration, and invasion of EC cell lines HEC-1B and KLE cells. The oncogenic activity of CARLo-5 was also confirmed with in vivo data. Mechanistically, CARLo-5 could affect the expression of CDK/CDKN1A and MMP2/9, which have been reported to be regulated by CARLo-5 and associated with cell cycle and motility. In conclusion, this study is the first to discover the biological function and mechanism of CARLo-5 in regulating the biological characteristics of EC cells. Targeting CARLo-5 and its pathway might provide new biomarkers or potential therapies target for patients with EC. Environ. Mol. Mutagen. 61:256-265, 2020. © 2019 Wiley Periodicals, Inc.

lncRNA SNHG5 Modulates Endometrial Cancer Progression via the miR-25-3p/BTG2 Axis.

Endometrial carcinoma (EC) is one of the most common malignancies of the female genital tract, although the mechanisms of EC initiation and development remain incompletely understood. In this study, we demonstrated that the noncoding RNA SNHG5 can inhibit the proliferation, migration, and invasion of EC cells by suppressing the expression of its putative target miR-25-3p. Overexpression of miR-25-3p significantly promoted the proliferation, migration, and invasion of EC cells. In addition, we showed that miR-25-3p represses the expression of BTG2 by directly binding to the 3'-UTR of BTG2 mRNA. Furthermore, increased miR-25-3p expression and decreased SNHG5 and BTG2 expression were observed in EC tissues, and the expression of SNHG5 was negatively correlated to that of miR-25-3p but positively correlated to that of BTG2. In summary, for the first time, we report that the SNHG5/miR-25-3p/BTG2 axis plays an important role in EC progression and is of great potential clinical significance for EC diagnosis and therapy.

The rs6983267 SNP and long non-coding RNA CARLo-5 are associated with endometrial carcinoma.

The single nucleotide polymorphism (SNP) rs6983267 and cancer-associated region long non-coding RNA (CARLo-5) are associated with various human cancers. This study aimed to investigate the expression of CARLo-5 in endometrial carcinoma (EC) and its relationship with clinicopathological features and patient survival. The association of the rs6983267 SNP with EC risk and its involvement in the regulation of CARLo-5 expression in EC were investigated. The rs6983267 SNP was genotyped by polymerase chain reaction (PCR) and ligase detection reaction in 543 EC patients and 584 controls. The expression of CARLo-5 in 108 EC tissues and 66 normal endometrial tissues (NETs) was determined using quantitative real-time PCR. The genotype and allele distributions of the rs6983267 SNP differed significantly between patients and controls. There was a significant correlation between the rs6983267 genotypes and lymph node metastasis of EC patients (P = 0.026). CARLo-5 expression was significantly higher in EC tissues than in NETs (P < 0.001) and significantly associated with FIGO stage (P = 0.029) and lymph node metastasis (P = 0.030). Patients with high CARLo-5 expression had significantly shorter overall survival than those with low CARLo-5 expression (P = 0.003). The rs6983267 genotype was significantly correlated with CARLo-5 expression (P < 0.05). In conclusion, CARLo-5 was identified as a pro-oncogenic lncRNA that may play an important role in EC progression and represent a prognostic marker for EC. The expression of CARLo-5 was significantly correlated with the rs6983267 genotype associated with increased susceptibility to EC. Environ. Mol. Mutagen. 57:508-515, 2016. © 2016 Wiley Periodicals, Inc.

Laparoscopic vaginoplasty using a single peritoneal flap: 10 years of experience in the creation of a neovagina in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

OBJECTIVE: To assess anatomical and functional outcomes of a novel laparoscopic vaginoplasty technique using a single peritoneal flap (SPF) in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: Prospective follow-up study. SETTING: University-based tertiary-care hospital. PATIENT(S): Patients with MRKH syndrome (n = 83) and randomly selected frequency-matched age-comparable healthy women serving as controls (n = 85). INTERVENTION(S): From March 2004 to March 2014, a total of 83 patients with MRKH syndrome underwent laparoscopic vaginoplasty using an SPF. MAIN OUTCOME MEASURE(S): Intraoperative parameters, postoperative parameters, and anatomical outcomes were recorded. The functional results of patients who became sexually active were assessed using the Female Sexual Function Index (FSFI) questionnaire and were compared with those of the controls. RESULT(S): Laparoscopic vaginoplasty using an SPF was successfully performed in all 83 patients, with no intraoperative complications. The mean operative time and intraoperative blood loss were, respectively, 71.2 ± 18.9 minutes and 88.5 ± 57.2 ml. The mean length and width of the neovagina at the 6-month follow-up examination were, respectively, 8.2 ± 0.8 cm and 3.0 ± 0.6 cm. Anatomical success was achieved in all patients. At 12 months after surgery, functional success, as assessed by the FSFI questionnaire, was achieved in 95.3% of patients. The FSFI scores did not differ significantly between patients with MRKH and healthy women in a control group. CONCLUSION(S): Laparoscopic vaginoplasty using an SPF may be a feasible and effective approach that has satisfactory anatomical and functional outcomes for patients with MRKH syndrome.

Comparison of two laparoscopic peritoneal vaginoplasty techniques in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the technical feasibility and long-term anatomical and functional outcomes of a novel laparoscopic vaginoplasty using single peritoneal flap (SPF) and Davydov's laparoscopic technique in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. METHODS: From September 2004 to September 2013, a comparative study was conducted of 98 patients with MRKH syndrome who underwent either laparoscopic vaginoplasty using SPF (SPF group, 62 cases) or Davydov's laparoscopic technique (Davydov group, 36 cases) in a university-based tertiary care hospital. Intraoperative and postoperative parameters and anatomical examination findings of the two groups were compared. Functional results were assessed using the Female Sexual Function Index (FSFI). RESULTS: All surgical procedures were performed successfully, with no intraoperative complications in either group. Patients in the SPF group had a significantly shorter operative time and less intraoperative blood loss than patients in the Davydov group. The postoperative course was identical for all patients in the two groups. The mean length and width of the neovagina in the two groups at hospital discharge, the 6-month follow-up, and the 12-month follow-up did not differ significantly. There were no significant differences between the groups with regard to the postoperative FSFI scores at 12 months after surgery. CONCLUSIONS: Although the long-term anatomical and functional outcomes of the two laparoscopic peritoneal vaginoplasty techniques are similar, laparoscopic vaginoplasty using SPF, which has many advantages and is easily performed by the gynecologist, is a more feasible and effective approach to creating a neovagina in patients with MRKH syndrome.

Genetic variation of the E-cadherin gene is associated with primary infertility in patients with ovarian endometriosis.

OBJECTIVE: To explore the association between the genetic variant of E-cadherin gene and endometriosis-related infertility. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): Five hundred eighty-nine women with ovarian endometriosis including 127 patients with primary infertility and 589 female controls in northern China. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Single nucleotide polymorphisms (SNPs) in the promoter region, exons, and the 3' untranslated region of the E-cadherin gene were identified by direct sequencing in patients with ovarian endometriosis and with polymerase chain reaction (PCR). Six candidate SNPs (rs16260, rs28372783, rs1801552, rs1801026, rs8049282, and rs13689) were genotyped by PCR and ligase detection reaction. RESULT(S): The results revealed a significant association of rs8049282 SNP on E-cadherin gene with endometriosis-related infertility. When compared with control women or endometriosis patients who had a history of successful fertility, the CC genotype of rs8049282 may significantly increase the risk of primary infertility in patients with ovarian endometriosis (adjusted odds ratio [OR] = 2.70, 95% confidence interval [CI] 1.45-5.00; OR = 2.54, 95% CI 1.45-4.44, respectively). CONCLUSION(S): Our results suggested that genetic variants on the E-cadherin gene may be involved in endometriosis-related infertility. The rs8049282 SNP of the E-cadherin gene may be a potential molecular marker for the development of primary infertility in northern Chinese women with ovarian endometriosis.

Optimization of reference genes for normalization of the quantitative polymerase chain reaction in tissue samples of gastric cancer.

For an exact comparison of mRNA transcription in different samples or tissues with real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), it is crucial to select a suitable internal reference gene. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and beta-actin (ACTB) have been frequently considered as house-keeping genes to normalize for changes in specific gene expression. However, it has been reported that these genes are unsuitable references in some cases, because their transcription is significantly variable under particular experimental conditions and among tissues. The present study was aimed to investigate which reference genes are most suitable for the study of gastric cancer tissues using qRT-PCR. 50 pairs of gastric cancer and corresponding peritumoral tissues were obtained from patients with gastric cancer. Absolute qRT-PCR was employed to detect the expression of GAPDH, ACTB, RPII and 18sRNA in the gastric cancer samples. Comparing gastric cancer with corresponding peritumoral tissues, GAPDH, ACTB and RPII were obviously up-regulated 6.49, 5.0 and 3.68 fold, respectively. Yet 18sRNA had no obvious expression change in gastric cancer tissues and the corresponding peritumoral tissues. The expression of GAPDH, ß-actin, RPII and 18sRNA showed no obvious changes in normal gastric epithelial cells compared with gastric cancer cell lines. The carcinoembryonic antigen (CEA), a widely used clinical tumor marker, was used as a validation gene. Only when 18sRNA was used as the normalizing gene was CEA obviously elevated in gastric cancer tissues compared with peritumoral tissues. Our data show that 18sRNA is stably expressed in gastric cancer samples and corresponding peritumoral tissues. These observations confirm that there is no universal reference gene and underline the importance of specific optimization of potential reference genes for any experimental condition.

Association between genetic variants of the VEGFR-2 gene and the risk of developing endometriosis in Northern Chinese Women.

AIM: To investigate the association of tag single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor 2 (VEGFR-2) gene with susceptibility to endometriosis. METHODS: This study comprised 571 patients with endometriosis and 580 women in the control group. Five tag SNPs in the VEGFR-2 gene were selected using a Haploview program, and those SNPs were genotyped by a method of polymerase chain reaction and ligase detection reaction. RESULTS: Statistical results show that there was a significant difference in the genotype and allele distribution of the 1192C/T polymorphism between the disease group and the control group (p = 0.041 and 0.017). The women carrying the T allele (C/T+T/T genotype) had a lower risk of developing endometriosis compared with the women with the C/C genotype (OR 0.75, 95% CI 0.57-0.99). There was no significant difference in the allele and genotype distribution of four other tag SNPs (1719T/A, +31C/T, IVS25-92A/G and IVS6+​54C/T) between the disease group and the control group (all p > 0.05). CONCLUSIONS: Our results suggested that the 1192C/T polymorphisms on the VEGFR-2 gene might affect the risk of developing endometriosis in Northern Chinese women of Han ethnicity.

[Study on the association of SNPs of MMP-2 and TIMP-2 genes with the risk of endometriosis and adenomyosis].

OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs) in matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) with the risk of endometriosis and adenomyosis. METHODS: Genotypes of MMP-2 and TIMP-2 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among 298 endometriosis patients, 180 adenomyosis patients and 324 matched control women. RESULTS: No significant difference was found in allele frequencies and genotype distributions of MMP-2 -1306C/T polymorphism between endometriosis patients and control women (P> 0.05). However, there were significant differences in genotype and allele distributions of MMP-2 -1306C/T polymorphism between adenomyosis patients and control women (P< 0.05). Compared with CT+TT genotypes, CC genotype significantly increases the risk of adenomyosis, with an odds ratio of 1.83 (95% CI was 1.13-2.96). No significant difference was shown in allele frequencies and genotype distributions of the MMP-2 -735C/T polymorphism among the three groups (P>0.05). MMP-2 -1306C/T and -735C/T polymorphisms displayed linkage disequilibrium (D'=0.74). There was no significant difference in haplotype distributions of the two MMP-2 SNPs among the three groups ( P> 0.05). No significant difference was found in allele frequencies of TIMP-2 -418G/C polymorphism among the three groups (P> 0.05). However, the frequency of TIMP-2 CC genotype in endometriosis patients (0.7%) was significantly lower than that in the control women (3.7%) (P< 0.05). CONCLUSION: The C allele of MMP-2 -1306C/T polymorphism did not modify the risk of developing endometriosis but significantly increase the risk of developing adenomyosis. The MMP-2 -735C/T and TIMP-2 -418G/C polymorphisms were not associated with the risk of developing endometriosis or adenomyosis.

[Association of SNPs in the promoter of MMP-2 and TIMP-2 genes with epithelial ovarian cancer].

The association between single nucleotide polymorphisms (SNPs) in the promoter region of MMP-2 and TIMP-2 genes and the risk of epithelial ovarian cancer was investigated. MMP-2 C-1306T, C-735T and TIMP-2 G-418C SNPs were genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis in 246 patients with epithelial ovarian cancer and 324 healthy women as control. Results showed no significant difference between the patient and control groups in allele or genotype distributions of MMP-2 C-1306T (P=0.55 and P=0.42). However, the frequencies of the C allele and the C/C genotype of the MMP-2 C-735T were significantly higher in ovarian cancer patients (80.7% and 66.7%) than those in healthy controls (75.5% and 55.9%). Compared with the T/T+C/T genotypes, the C/C genotype significantly increased the risk of ovarian cancer (OR=1.58, 95%CI=1.12-2.23). Stratification analysis showed that subjects carrying C/C genotype were significantly associated with the risk of endometrioid ovarian cancer and with ovarian cancer in subjects that were 50 or older, with odds ratio at 1.69 (95%CI=1.03-2.79) and 1.71 (95%CI=1.14-2.57), respectively. Haplotype analysis showed that the frequencies of four haplotypes (T(-1306)-T(-735), T(-1306)-C(-735), C(-1306)-T(-735) and C(-1306)-C(-735)) of MMP-2 C-1306T and C-735T were not significantly different between the patient and control groups (P=0.24). The allele and genotype frequencies of TIMP-2 G-418C were not significantly different between the patient and control groups (P=0.33 and P=0.47). But TIMP-2 -418G/G genotype was associated with a trend for endometrioid ovarian cancer by stratification analysis according to histological subtypes (OR=1.62, 95%CI=0.94-2.78). Thus, the study suggested that the C/C genotype of the C-735T SNP in the promoter region of MMP-2 gene may be a potential risk factor for epithelial ovarian cancer, but the C-1306T SNP may have no association with the risk of epithelial ovarian cancer. The TIMP-2 G-418C SNP may be associated with the risk of different histological subtypes of epithelial ovarian cancer.

Polymorphisms in the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 and the risk of human adenomyosis.

The matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may contribute to the development of adenomyosis. The aim of the present study was to investigate whether three single nucleotide polymorphisms (SNPs) in the promoter regions of MMP-2 (-1306C/T and -735C/T) and TIMP-2 (-418G/C) genes were related to the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 180 adenomyosis patients and 324 frequency-matched control women in a Chinese population. There were significant differences in allele frequencies and genotype distributions of the MMP-2 -1306C/T polymorphism between patients and control women (P = 0.01 and 0.04, respectively). The frequency of C allele in patients (92.2%) was significantly higher than in the controls (87.0%) (P = 0.01). Compared with the C/T+T/T genotypes, the C/C genotype could significantly increase the risk of adenomyosis development, with an odds ratio of 1.83 (95% CI = 1.13-2.96). However, no statistically significant difference was found in allele frequencies and genotype distributions of MMP-2 -735C/T and TIMP-2 -418G/C SNPs between the two groups (all P values > 0.05). Two polymorphisms of MMP-2 displayed linkage disequilibrium (D' = 0.74). The haplotype analysis suggested no significant association of four haplotypes with the risk of adenomyosis development. Our results indicated an association of MMP-2 -1306C/T polymorphism with the risk of adenomyosis, suggesting a potential role in adenomyosis development in North Chinese women.

Association of polymorphisms of the MMP-2 and TIMP-2 genes with the risk of endometriosis in North Chinese women.

We investigated whether three polymorphisms in the matrix metalloproteinase-2 (MMP-2; -1306C-->T and -735C-->T) and tissue inhibitor of metalloproteinase-2 (TIMP-2; -418G-->C) genes were related to the risk of endometriosis in reproductive-aged women with and without endometriosis. Our results indicate that the TIMP-2 -418C/C homozygote may be a protective factor against the development of endometriosis in North Chinese women.