Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: Revisiting old hypotheses

Fleming, Jean S.; Beaugié, Clare R.; Haviv, Izhak; Chenevix-Trench, Georgia; Tan, Olivia L.

doi:10.1016/j.mce.2005.09.014

Cited by 169 publications

(138 citation statements)

References 173 publications

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“…(Table1) Analysis of risk factors showed a significant association between hormonal factors and ovarian malignancy. Age at menarche less than 13 years and period of ovulation more than 33 years in post-menopausal women were found to be significant risk factors for ovarian cancer in our study.This finding is consistent with incessant ovulation hypothesiswhich postulates that the rupture and subsequent rapid proliferation of the ovarian surface epithelium with ovulation may lead to malignant transformation of ovarian epithelium 8,9 .Various studies found an increase of 1year worth of ovulationwas associated with a 2 to 6% increase in risk of ovarian malignancy 10,11 . In this study themean age of menopause was significantly delayed in cases (47.7 years vs44.6years) than controls (p-0.05).…”

Section: Resultssupporting

confidence: 89%

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Epidemiological Risk Factors for Primary Ovarian Malignancy in Indian Population- A Case Control Study from a Tertiary Care Centre in Kerala

B¹

2017

jmscr

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Section: Resultssupporting

confidence: 89%

“…Compared to nulliparous women, parous women are at reduced risk of ovarian cancer with a significant risk reduction by one birth event 8,11 . This is because, exposure to high progestin levels, whether through pregnancy or exogenous hormones, reduces ovarian cancer risk.…”

Section: Resultsmentioning

confidence: 99%

Epidemiological Risk Factors for Primary Ovarian Malignancy in Indian Population- A Case Control Study from a Tertiary Care Centre in Kerala

B¹

2017

jmscr

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“…Advocates of this so-called incessant ovulation hypothesis argue that repeated rupture of the ovarian surface during ovulation and subsequent repair by OSE proliferation may increase the frequency at which mutations arise. However, some have deemed this model too simplistic, since neither the effects of reproductive hormones nor acute inflammation is taken into account, both of which may be mutagenic (Bose, 2005;Bukulmez and Arici, 2000;Cramer and Welch, 1983;Fleming et al, 2006;Konishi, 2006;Mohle et al, 1985;Ness and Cottreau, 1999;.…”

Section: Disease Etiologymentioning

confidence: 99%

Role of p53 and Rb in Ovarian Cancer

Corney

Flesken‐Nikitin

Choi

et al.

Advances in Experimental Medicine and Biology

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Ovarian cancer remains a major health concern worldwide, primarily in postmenopausal women. Among the most common genetic alterations in human sporadic epithelial ovarian cancer (EOC) are p53 mutations, defective retinoblastoma (RB) pathway (p16 INK4a /RB) and activation of oncogenes such as c-myc, K-ras and Akt. Although these alterations are frequently associated with poor clinical prognosis, their specific contributions to EOC formation remain unclear. In order to gain a better understanding of the roles of these proteins in vivo, a number of mouse models have been generated, largely based upon inducing specific genetic lesions in the ovarian surface epithelium from which the majority of carcinomas are thought to arise in humans. Here, we review the role of tumor suppressor p53 and the Rb pathway in EOC with particular attention to association of p53 to high grade serous carcinomas as opposed to low grade and benign tumors. We also provide an overview of the utility and application of genetically engineered mouse models, in particular towards rational drug design and development of improved imaging techniques in ovarian cancer.

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“…The complexity of EOC appears to indicate that the ovarian surface epithelium as well as the Fallopian tube epithelium are involved in the development of this disease (10). The ovarian surface epithelium as the origin for EOC is the oldest hypothesis and has been associated with the high frequency of ovulation in women (19)(20)(21). During each ovulation, this epithelium is disrupted when the mature oocyte is expelled from the ovary and inflammatory processes are then required to repair it (17,22).…”

Section: Pathology and Origin Of Eoc In Humansmentioning

confidence: 99%

Advantages of the avian model for human ovarian cancer

Bernardo

Þorsteinsdóttir

Mummery

2015

Molecular and Clinical Oncology

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Abstract. Ovarian cancer (OC) is the most lethal gynecological cancer. Early detection of OC is crucial for providing efficient treatment, whereas high mortality rates correlate with late detection of OC, when the tumor has already metastasized to other organs. The most prevalent type of OC is epithelial OC (EOC). Models that have been used to study EOC include the fruit fly, mouse and laying hen, in addition to human EOC cells in 3D culture in vitro. These models have helped in the elucidation of the genetic component of this disease and the development of drug therapies. However, the histological origin of EOC and early markers of the disease remain largely unknown. In this study, we aimed to review the relative value of each of the different models in EOC and their contributions to understanding this disease. It was concluded that the spontaneous occurrence of EOC in the adult hen, the prolific ovulation, the similarity of metastatic progression with that in humans and the advantages of using the chicken embryo for modelling the development of the reproductive system, renders the hen particularly suitable for studying the early development of EOC. Further investigation of this avian model may contribute to a better understanding of EOC, improve clinical insight and ultimately contribute to decreasing its mortality rates among humans.

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Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: Revisiting old hypotheses

Cited by 169 publications

References 173 publications

Epidemiological Risk Factors for Primary Ovarian Malignancy in Indian Population- A Case Control Study from a Tertiary Care Centre in Kerala

Epidemiological Risk Factors for Primary Ovarian Malignancy in Indian Population- A Case Control Study from a Tertiary Care Centre in Kerala

Role of p53 and Rb in Ovarian Cancer

Advantages of the avian model for human ovarian cancer

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