Browsing by Subject "ENDOMETRIOSIS"

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  • Zhang, G.; Feenstra, B.; Bacelis, J.; Liu, X.; Muglia, L. M.; Juodakis, J.; Miller, D. E.; Litterman, N.; Jiang, P. -P.; Russell, L.; Hinds, D. A.; Hu, Y.; Weirauch, M. T.; Chen, X.; Chavan, A. R.; Wagner, G. P.; Pavlicev, M.; Nnamani, M. C.; Maziarz, J.; Karjalainen, M. K.; Ramet, M.; Sengpiel, V.; Geller, F.; Boyd, H. A.; Palotie, A.; Momany, A.; Bedell, B.; Ryckman, K. K.; Huusko, J. M.; Forney, C. R.; Kottyan, L. C.; Hallman, M.; Teramo, K.; Nohr, E. A.; Smith, G. Davey; Melbye, M.; Jacobsson, B.; Muglia, L. J. (2017)
    BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0x10(-8)) or an association with suggestive significance (P<1.0x10(-6)) in the discovery set. RESULTS In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.
  • Hollestelle, Antoinette; van der Baan, Frederieke H.; Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K.; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Barrowdale, Daniel; Bean, Yukie T.; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Bruning, Thomas; Butzow, Ralf; Leminen, Arto; Muranen, Taru A.; Nevanlinna, Heli; Pelttari, Liisa M.; Ovarian Canc Assoc Consortium; Breast Canc Assoc Consortium; Consortium Modifiers BRCA1 & BRCA2; Australian Ovarian Canc Study Grp; Breast Cancer Family Register; EMBRACE; GEMO Study Collaborators; GENICA Network; HEBON; kConFab Investigators; SWE-BRCA (2016)
    Objective. Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods. Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results. We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 034, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions. rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. (C) 2015 Elsevier Inc. All rights reserved.
  • Pynnä, Kristiina; Räsänen, Pirjo; Roine, Risto P.; Vuorela, Piia; Sintonen, Harri (2021)
    Objectives The impact of benign gynecological conditions on life of women and on costs for the society is high. The purpose of this study is to gain knowledge and understanding of costs of the treatment of these disorders in order to be able to improve the clinical care processes, gain insight into feasible savings opportunities and to allocate funds wisely. Methods The healthcare processes of 311 women attending university or community hospitals in the Helsinki and Uusimaa Hospital District between June 2012 and August 2013 due to a benign gynecological condition were followed up for two years and treatment costs analysed. Results Total direct hospital costs averaged 689euro at six months and 2194euro at two years. The most expensive treatment was that of uterine fibroids in the short term and that of endometriosis and fibroids later on. Costs did not depend on hospital size. Surgical operations caused nearly half of hospital costs. Productivity loss caused biggest expenses outside of the hospital. LNG-IUD (levonorgestrel-releasing intrauterine device) accounted for the largest pharmaceutical costs for patients. Hospital treatment was associated with a reduced need for outpatient services during follow-up. Conclusions A majority of direct hospital costs arise over time. This stresses the need for prolonged healthcare management. To control costs, the need for repetitive doctors' appointments, monitoring tests, and ward treatments should be carefully evaluated. Procedures not needing an operation theatre (for example hysteroscopy for polypectomy), should be done ambulatorily.
  • Soritsa, Deniss; Teder, Hindrek; Roosipuu, Retlav; Tamm, Hannes; Laisk-Podar, Triin; Soplepmann, Pille; Altraja, Alan; Salumets, Andres; Peters, Maire (2018)
    Background: Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML. Case presentation: We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay. Conclusions: We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases.
  • Boussios, Stergios; Mikropoulos, Christos; Samartzis, Eleftherios; Karihtala, Peeter; Moschetta, Michele; Sheriff, Matin; Karathanasi, Afroditi; Sadauskaite, Agne; Rassy, Elie; Pavlidis, Nicholas (2020)
    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women. Two-thirds of patients present at advanced stage at diagnosis, and the estimated 5 year survival rate is 20-40%. This heterogeneous group of malignancies has distinguishable etiology and molecular biology. Initially, single-gene sequencing was performed to identify germline DNA variations associated with EOC. However, hereditary EOC syndrome can be explained by germline pathogenic variants (gPVs) in several genes. In this regard, next-generation sequencing (NGS) changed clinical diagnostic testing, allowing assessment of multiple genes simultaneously in a faster and cheaper manner than sequential single gene analysis. As we move into the era of personalized medicine, there is evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in breast cancer gene 1 and 2 (BRCA1/2) mutation carriers. Furthermore, extensive preclinical data supported the development of aurora kinase (AURK) inhibitors in specific tumor types, including EOC. Their efficacy may be optimized in combination with chemotherapeutic or other molecular agents. The efficacy of metformin in ovarian cancer prevention is under investigation. Certain mutations, such as ARID1A mutations, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which are specific in ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC), may offer additional therapeutic targets in these clinical entities. Malignant ovarian germ cell tumors (MOGCTs) are rare and randomized trials are extremely challenging for the improvement of the existing management and development of novel strategies. This review attempts to offer an overview of the main aspects of ovarian cancer, catapulted from the molecular mechanisms to therapeutic considerations.