Association between ovarian cancer and advanced endometriosis.
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ABSTRACT:
SUBMITTER: Matalliotakis M
PROVIDER: S-EPMC5920362 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Association between ovarian cancer and advanced endometriosis.
Matalliotakis Michail M Matalliotaki Charoula C Goulielmos George N GN Patelarou Evridiki E Tzardi Maria M Spandidos Demetrios A DA Arici Aydin A Matalliotakis Ioannis I
Oncology letters 20180316 5
We retrospectively analyzed clinicopathological data in two different countries over the past years on the association between ovarian endometriosis and ovarian carcinoma. Medical and pathological reports were evaluated from 1,000 patients with endometriosis from two different geographical areas. The prevalence and women characteristics of cases were analyzed. Endometriosis-associated ovarian cancer was present in 20 (2%) cases, among the study subjects. The observed prevalence was 12 (60%) for ...[more]
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Project description:Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
| S-EPMC4581608 | biostudies-literature
Project description:To investigate the association between endometriosis, tubal ligation, hysterectomy and epithelial ovarian cancer. Relevant published literatures were searched in PubMed, ProQuest, Web of Science and Medline databases during 1995-2016. Heterogeneity was evaluated by I² statistic. Publication bias was tested by funnel plot and Egger's test. Odds ratio and 95% CI were used to assess the association strength. The statistical analyses in this study were accomplished by STATA software package. A total of 40,609 cases of epithelial ovarian cancer and 368,452 controls in 38 publications were included. The result suggested that endometriosis was associated with an increased risk of epithelial ovarian cancer (OR = 1.42, 95% CI = 1.28-1.57), tubal ligation was associated with a decreased risk of epithelial ovarian cancer (OR = 0.70, 95% CI = 0.60-0.81), while hysterectomy show no relationship with epithelial ovarian cancer (OR = 0.97, 95% CI = 0.81-1.14). A stratified analysis showed there were associations between endometriosis and the increased risk of epithelial ovarian cancer for studies conducted in USA and Europe. Meanwhile, there were associations between tubal ligation and the decreased risk of epithelial ovarian cancer for studies conducted in USA, Asia, Europe and Australia. The result indicated that endometriosis was a risk factor of epithelial ovarian cancer whereas tubal ligation was a protective risk factor of epithelial ovarian cancer, hysterectomy may have no relationship with epithelial ovarian cancer.
| S-EPMC5129348 | biostudies-literature
Project description:OBJECTIVE:To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. DESIGN:Pooled genetic analysis. SETTING:University hospital. PATIENT(S):Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Endometriosis-associated genetic variation and ovarian cancer. RESULT(S):There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. CONCLUSION(S):By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
| S-EPMC5068352 | biostudies-literature
Project description:AimEndometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue.MethodsDue to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis.ResultsIn total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability.ConclusionsITGA7, ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets.KEY MESSAGEThis manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis.This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis.We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.
| S-EPMC8381947 | biostudies-literature
Project description:BackgroundEndometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.MethodsData from 13 ovarian cancer case-control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.Findings13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43-3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39-3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67-2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69-1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97-1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95-1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84-1·48, p=0·45).InterpretationClinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.FundingOvarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.
| S-EPMC3664011 | biostudies-literature
Project description:OBJECTIVE:To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC). DESIGN:Case-control study. SETTING:University hospital research laboratory. PATIENT(S):Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries. INTERVENTION(S):Ovarian tissue samples were collected from surgical procedures. MAIN OUTCOME MEASURE(S):We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction. RESULT(S):We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries. CONCLUSION(S):That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis.
| S-EPMC4426869 | biostudies-literature
Project description:The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.
| S-EPMC5007828 | biostudies-literature
Project description:ImportanceBreastfeeding has been associated with a reduced risk of epithelial ovarian cancer in multiple studies, but others showed no association. Whether risk reduction extends beyond that provided by pregnancy alone or differs by histotype is unclear. Furthermore, the observed associations between duration and timing of breastfeeding with ovarian cancer risk have been inconsistent.ObjectiveTo determine the association between breastfeeding (ie, ever/never, duration, timing) and ovarian cancer risk overall and by histotype.Design, setting, and participantsA pooled analysis of parous women with ovarian cancer and controls from 13 case-control studies participating in the Ovarian Cancer Association Consortium was performed. Odds ratios (ORs) and 95% CIs of the overall association were calculated using multivariable logistic regression and polytomous logistic regression for histotype-specific associations. All data were collected from individual sites from November 1989 to December 2009, and analysis took place from September 2017 to July 2019.ExposuresData on breastfeeding history, including duration per child breastfed, age at first and last breastfeeding, and years since last breastfeeding were collected by questionnaire or interview and was harmonized across studies.Main outcomes and measuresDiagnosis of epithelial ovarian cancer.ResultsA total of 9973 women with ovarian cancer (mean [SD] age, 57.4 [11.1] years) and 13 843 controls (mean [SD] age, 56.4 [11.7] years) were included. Breastfeeding was associated with a 24% lower risk of invasive ovarian cancer (odds ratio [OR], 0.76; 95% CI, 0.71-0.80). Independent of parity, ever having breastfed was associated with reduction in risk of all invasive ovarian cancers, particularly high-grade serous and endometrioid cancers. For a single breastfeeding episode, mean breastfeeding duration of 1 to 3 months was associated with 18% lower risk (OR, 0.82; 95% CI, 0.76-0.88), and breastfeeding for 12 or more months was associated with a 34% lower risk (OR, 0.66; 95% CI, 0.58-0.75). More recent breastfeeding was associated with a reduction in risk (OR, 0.56; 95% CI, 0.47-0.66 for <10 years) that persisted for decades (OR, 0.83; 95% CI, 0.77-0.90 for ≥30 years; P for trend = .02).Conclusions and relevanceBreastfeeding is associated with a significant decrease in risk of ovarian cancer overall and for the high-grade serous subtype, the most lethal type of ovarian cancer. The findings suggest that breastfeeding is a potentially modifiable factor that may lower risk of ovarian cancer independent of pregnancy alone.
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Project description:Endometriosis, a largely benign, chronic inflammatory disease, is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors. We aimed to identify plasma miRNAs that can be used to differentiate patients with endometriosis and ovarian cancer from healthy individuals.We conducted a two-stage exploratory study to investigate the use of plasma miRNA profiling to differentiate between patients with endometriosis, patients with endometriosis-associated ovarian cancer (EAOC), and healthy individuals. In the first stage, using global profiling of more than 1,000 miRNAs via reverse transcriptase quantitative PCR (RT-qPCR) in a 20-patient initial screening cohort, we identified 23 candidate miRNAs, which are differentially expressed between healthy controls (n = 6), patients with endometriosis (n = 7), and patients with EAOC (n = 7) based on the fold changes. In the second stage, the 23 miRNAs were further tested in an expanded cohort (n = 88) of healthy individuals (n = 20), endometriosis (n = 33), EAOC (n = 14), and serous ovarian cancer cases (SOC; n = 21, included as controls).We identified three distinct miRNA signatures with reliable differential expression between healthy individuals, patients with endometriosis, and patients with EAOC. When profiled against the control SOC category, our results revealed different miRNAs, suggesting that the identified signatures are reflective of disease-specific pathogenic mechanisms. This was further supported by the fact that the majority of miRNAs differentially expressed in human EAOCs were mirrored in a double transgenic mouse EAOC model.Our study reports for the first time that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases.
| S-EPMC3596045 | biostudies-literature
Project description:Mechanisms of immune dysregulation associated with advanced tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear-cell ovarian tumors partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here a comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC).RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n = 32), benign endometriosis (n = 30), atypical endometriosis (n = 15), and EAOC (n = 43). Serous tumors (n = 15) were included as nonendometriosis-associated controls. The immune microenvironment was profiled using Nanostring and the nCounter GX Human Immunology Kit, comprising probes for a total of 511 immune genes.One third of the patients with endometriosis revealed a tumor-like inflammation profile, suggesting that cancer-like immune signatures may develop earlier, in patients classified as clinically benign. Gene expression analyses revealed the complement pathway as most prominently involved in both endometriosis and EAOC. Complement proteins are abundantly present in epithelial cells in both benign and malignant lesions. Mechanistic studies in ovarian surface epithelial cells from mice with conditional (Cre-loxP) mutations show intrinsic production of complement in epithelia and demonstrate an early link between Kras- and Pten-driven pathways and complement upregulation. Downregulation of complement in these cells interferes with cell proliferation.These findings reveal new characteristics of inflammation in precursor lesions and point to previously unknown roles of complement in endometriosis and EAOC.
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