The risk of cancer and the role of parity among women with endometriosis

Melin, Anna-Sofia; Sparén, Pär; Bergqvist, Agneta

doi:10.1093/humrep/dem209

Cited by 133 publications

(50 citation statements)

References 33 publications

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“…Other risk factors for ovarian cancer include age over 45 years (and especially over 60 years), nulliparity, infertility, low parity, early menarche and late menopause or normal menopause with hot flushes [17][18][19]. Chances of developing ovarian cancer are also greater with long term use of post-menopausal oestrogen-only hormone replacement therapy, high body mass index, endometriosis, and perineal talcum powder application [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Awareness of Signs and Symptoms of Ovarian Cancer among Gynecology Nurses in a Large Teaching Hospital in the UK (Awareness of Ovarian Cancer among Gynecology Nurses)

Hay¹,

Abdul²

2015

J Women’s Health Care

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Background: The overall mortality of ovarian cancer is high because of its late presentation, with over 80% of patients presenting with advanced disease largely due to the vague symptoms in its early stages. Ninety percent of those diagnosed with early stage ovarian cancer were symptomatic before diagnosis. It is therefore important that women are aware of the signs and symptoms of ovarian cancer as early detection greatly improves the chances of successful treatment, and because nurses play an important helping role which is useful in public education and awareness, they should be aware of the red flags of ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

Awareness of Signs and Symptoms of Ovarian Cancer among Gynecology Nurses in a Large Teaching Hospital in the UK (Awareness of Ovarian Cancer among Gynecology Nurses)

Hay¹,

Abdul²

2015

J Women’s Health Care

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“…Whereas innate immunity has been addressed repeatedly (Maeda et al, 2002;Montagna et al, 2008;Tariverdian et al, 2007;Yamamoto et al, 2008), there have been few studies of the role of adaptive, antigen-specific immunity in this disease (Antsiferova et al, 2005;Podgaec et al, 2007;Szyllo et al, 2003). Given the potential for the occurrence of ovarian cancer in a subset of endometriosis patients (Brinton et al, 1997;Kobayashi et al, 2007;Melin et al, 2007;Melin et al, 2006;Nagle et al, 2008;Ogawa et al, 2000;Olson et al, 2002;Prowse et al, 2006;Somigliana et al, 2006;Varma et al, 2004;Yoshikawa et al, 2000), the best target antigens to study are those that are present in both endometriosis and ovarian epithelial tumors. Several ovarian tumor-associated antigens have been defined and are currently being tested as antigen-specific immune therapies in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells

Budiu

Diaconu

Chrissluis

et al. 2009

Disease Models &Amp; Mechanisms

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SUMMARYEndometriosis is defined by the presence of tissue implants resembling endometrial glands outside of the uterus, at ectopic sites, frequently on the ovarian surface. The ectopic lesions are often invasive, resistant to therapy, and may predispose to endometrioid and clear cell ovarian tumors. The complex mechanisms leading to chronic endometriosis are mediated partly by impaired immune surveillance in the host. Although innate immunity has been addressed previously, the response of adaptive immune effectors to specific antigens has not been characterized, mostly because very few endometriosis antigens have been defined to date. We postulated that the mucin 1 (MUC1) glycoprotein, which is normally present on eutopic human endometrial glands and overexpressed in endometrioid and clear cell ovarian tumors, is also present in ectopic lesions of ovarian endometriosis. Furthermore, changes in MUC1 expression in endometriosis could promote adaptive anti-MUC1 immunity that might play a role in the malignant progression. To test our hypothesis, we crossed MUC1 transgenic mice, which express human MUC1 under the endogenous promoter, with the loxP-Stop-loxP-Kras G12D/+ (Kras) mice, in which endometriosis can be induced through Cre-loxP recombination. The double transgenic MUC1Kras mice develop benign, MUC1-positive ovarian lesions, closely resembling human endometriosis. Subsequent to disease induction, the mice generate high titers of IgM and IgG antibodies that are specific for MUC1. Antibodies appear early in disease and the predominance of the IgG1 subclass suggests Th2-driven immunity. Immune phenotyping revealed an accumulation of Foxp3+ CD4 regulatory T cells (Tregs) in the draining lymph nodes at late-stage disease. Furthermore, our observations in human endometriosis showed a similar recruitment of FOXP3+ CD4 T cells. Overall, our results reveal a Th2/Treg-dominant natural immunity in endometriosis with potential implications for cancer progression.

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“…Up to 10% of adult females and 40% of infertile women have the disease, which also exhibits comorbidity with several cancers (4,5). Endometriosis currently has no cure: hormonal therapies merely manage the disease with significant side effects, and surgery provides only temporary relief for many, with recurrence rates as great as 40% within 5 y postoperation (6).…”

mentioning

confidence: 99%

ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling

Miller¹,

Meyer²,

Beste

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM "sheddase" function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor-driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.cell signaling networks | metalloproteinase activity | cue-signal-response analysis | amphiregulin

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The risk of cancer and the role of parity among women with endometriosis

Cited by 133 publications

References 33 publications

Awareness of Signs and Symptoms of Ovarian Cancer among Gynecology Nurses in a Large Teaching Hospital in the UK (Awareness of Ovarian Cancer among Gynecology Nurses)

Awareness of Signs and Symptoms of Ovarian Cancer among Gynecology Nurses in a Large Teaching Hospital in the UK (Awareness of Ovarian Cancer among Gynecology Nurses)

A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells

ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling

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