Factors Related to Inflammation of the Ovarian Epithelium and Risk of Ovarian Cancer

Ness, Roberta B.; Grisso, Jeane Ann; Cottreau, Carrie; Klapper, Jennifer; Vergona, Ronald; Wheeler, James E.; Morgan, Mark A.; Schlesselman, James J.

doi:10.1097/00001648-200003000-00006

Cited by 317 publications

(247 citation statements)

References 36 publications

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“…After adjusting for age, number of pregnancies, family history of ovarian cancer, race, oral contraceptive use, tubal ligation, hysterectomy and breastfeeding; women with ovarian cancer were 1.7-fold more likely to have reported a history of endometriosis than controls. 15 These data are consistent with an earlier report of a 2.5-fold increased risk of ovarian cancer in endometriosis patients, with the risk increasing to 4.2-fold in those with a history of ovarian endometriosis. 16 However, despite the histological and epidemiological evidence linking these two diseases, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link involving common environmental, immunological, hormonal or genetic factors.…”

supporting

confidence: 92%

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Prowse

Manek

Varma

et al. 2006

Intl Journal of Cancer

146

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Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosisassociated ovarian cancers (EAOCs)-in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid 5 4; clear cell 5 6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs. ' 2006 Wiley-Liss, Inc.

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supporting

confidence: 92%

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Prowse

Manek

Varma

et al. 2006

Intl Journal of Cancer

146

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“…CXC chemokines in epithelial ovarian cancer Ness et al 2000, Fleming et al 2006, Son et al 2007, Coffelt & Scandurro 2008, Maccio & Madeddu 2012. As key mediators of inflammation, chemokines play two major roles: i) they are responsible for the recruitment and activation of immune cells into sites of malignancy (and possibly areas of pre-neoplastic growth) and ii) they mediate pro-and anti-angiogenic effects, processes required for the vascularisation and progression of tumours.…”

Section: Inflammation and The Ovarian Surface Epitheliummentioning

confidence: 99%

The emerging role of CXC chemokines in epithelial ovarian cancer

et al. 2012

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In recent years, chemokines have generated intense investigations due to their involvement in both physiological and pathological processes of inflammation, particularly in ovarian biology. The physiological process of ovulation in the normal ovary involves various chemokines that mediate the healing of the ruptured endometrium. It is now being reported that many of these chemokines are also associated with the cancer of the ovary. Chronic inflammation underlies the progression of ovarian cancer; therefore, it raises the possibility that chemokines are involved in the inflammatory process and mediate immune responses that may favour or inhibit tumour progression. Ovarian cancer is a gynaecological cancer responsible for highest rate of mortality in women. Although there have been several investigations and advances in surgery and chemotherapy, the survival rate for this disease remains low. This is mainly because of a lack of specific symptoms and biomarkers for detection. In this review, we have discussed the emerging role of the CXC chemokines in epithelial ovarian cancer (EOC). The CXC group of chemokines is gaining importance in the field of ovarian cancer for being angiostatic and angiogenic in function. While there have been several studies on the angiogenesis function, emerging research shows that ELR K CXC chemokines, CXCL9 and CXCL10, are angiostatic. Importantly, the angiostatic chemokines can inhibit the progression of EOC. Given that there are currently no biomarkers or specific therapeutic targets for the disease, these chemokines are emerging as promising targets for therapy.

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“…Factors related to inflammation of the OSE have been associated with increased risk of ovarian cancer (Ness and Cottreau, 1999;Ness et al, 2000) and exposure to anti-inflammatory agents has been shown to inhibit tumour invasion and protease production by ovarian carcinoma cells (Akhmedkhanov et al, 2001). It is therefore of obvious interest that all cell lines studied here appear to have largely lost their capacity to mount an inflammatory response to IL-1a in terms of increased 11bHSD-1 expression and hence increased formation of anti-inflammatory, proapoptotic glucocorticoids.…”

Section: Discussionmentioning

confidence: 96%

“…Repeated episodes of ovulation-associated injury and repair are presumed to underlie the high frequency of ovarian carcinoma arising from the OSE (Fathalla, 1971;Salazar et al, 1996), which account for 90% of all ovarian cancers (Ozols, 1991). Since ovulation is a natural inflammatory process (Espey, 1980a, b), factors related to inflammation of the OSE have been associated with increased risk of ovarian cancer (Ness and Cottreau, 1999;Ness et al, 2000). It is therefore critically important to understand how inflammatory cell damage is normally resolved in the OSE.…”

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confidence: 99%

Inflammation-associated gene expression is altered between normal human ovarian surface epithelial cells and cell lines derived from ovarian adenocarcinomas

et al. 2005

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Ovulation is believed to contribute to the development of ovarian cancers that derive from the ovarian surface epithelium (OSE). The process of ovulation is synonymous with inflammation and inflammatory cytokines such as interleukin-1a (IL-1a) have recently been shown to induce both inflammatory and anti-inflammatory responses in human OSE (HOSE) cells. In this study we directly compared levels of IL-1a-induced gene expression by analysing the levels of 11b-hydroxysteroid dehydrogenase (11bHSD) types 1 (11bHSD-1) and 2 (11bHSD-2), cyclooxygenase-2 (COX-2), IL-1 receptor (IL-1R) and glucocorticoid receptor a (GRa) mRNA between normal HOSE cells and cell lines derived from poorly differentiated (SKOV-3, BG-1, PEO-4) and well-differentiated (PEO-14) ovarian adenocarcinoma. In HOSE cell cultures, and to a lesser extent PEO-14 cells, the basal mRNA levels of COX-2 and 11bHSD-1 were relatively high and further shown to be induced in response to IL-1a (for HOSE cells; 420-fold, Po0.05 and PEO-14 cells; 43fold, Po0.05). However, whereas HOSE cells expressed a low level of 11bHSD-2 mRNA that was only mildly responsive to IL-1a (1.3-fold, Po0.001), all cell lines exhibited a higher basal level of 11bHSD-2 mRNA that was in some cases further stimulated in PEO-4 cells (five-fold; Po0.05) or suppressed in SKOV-3 cells (two-fold; Po0.01) in response to IL-1a. All cells tested expressed IL-1R and, with the exception of BG-1, GRa. These results indicate that cell lines derived from ovarian cancers have lost the ability to respond normally to inflammatory cytokines such as IL-1a. The finding that normal OSE cells, in contrast to cell lines derived from patients with ovarian adenocarcinoma, abundantly express 11bHSD-1 mRNA but are essentially devoid of 11bHSD-2 mRNA supports the concept that the pattern of 11bHSD isoform gene expression is a defining feature of neoplastic cellular transformation, which might have particular relevance to the ovary.

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Factors Related to Inflammation of the Ovarian Epithelium and Risk of Ovarian Cancer

Cited by 317 publications

References 36 publications

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

The emerging role of CXC chemokines in epithelial ovarian cancer

Inflammation-associated gene expression is altered between normal human ovarian surface epithelial cells and cell lines derived from ovarian adenocarcinomas

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