Benign Epithelial Ovarian Tumours—cancer Precursors or Markers for Ovarian Cancer Risk?

Jordan, Susan J.; Green, Adèle C.; Webb, Penelope M.

doi:10.1007/s10552-005-0370-y

Cited by 27 publications

(16 citation statements)

References 60 publications

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“…Consistent with this result, we observed in the NECC study of ovarian cancer the suggestion of an increased risk of the borderline serous subtype for women with PCOS (OR = 1.2; 95% CI 0.5–2.8) that was also stronger among overweight women [63]. Serous borderline ovarian tumors have been proposed to arise from benign ovarian tumors [68] and have higher androgen receptor levels than serous invasive tumors [52]. Furthermore, in a large European prospective cohort study, prediagnostic androstenedione was shown to increase risk of low-grade tumors (OR = 1.99; 95% CI = 0.98–4.06) but decrease risk of high grade tumors (OR = 0.75; 95% CI = 0.61–0.93) [57].…”

Section: Introductionsupporting

confidence: 64%

Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Harris

Terry

2016

Fertil Res and Pract

110

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BackgroundPolycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4–21% in reproductive aged women. The altered metabolic and hormonal environment among women with PCOS may increase their risk of some types of cancer.MethodsWe performed a comprehensive review of the literature using numerous search terms for all studies examining the associations between polycystic ovary syndrome and related characteristics and cancer published in English through October 2016. This review summarizes the epidemiological findings on the associations between PCOS and endometrial, ovarian, and breast cancers and discusses the methodological issues, complexities, and underlying mechanisms of these associations.ResultsWe identified 11 individual studies and 3 meta-analyses on the associations between PCOS and endometrial cancer, 8 studies and 1 meta-analysis for ovarian cancer, and 10 studies and 1 meta-analysis for breast cancer. Multiple studies reported that women with PCOS were at a higher risk for endometrial cancer; however, many did not take into account body mass index (BMI), a strong and well-established risk factor for endometrial cancer. The association with ovarian cancer was less clear, but a potentially increased risk of the borderline serous subtype was reported by two studies. No consistent association between PCOS risk and breast cancer was observed.ConclusionThe associations between PCOS and endometrial, ovarian, and breast cancer are complex, with the need to consider many methodological issues in future analyses. Larger well-designed studies, or pooled analyses, may help clarify these complex associations.

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Section: Introductionsupporting

confidence: 64%

Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Harris

Terry

2016

Fertil Res and Pract

110

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“…High BMI has been associated with benign ovarian tumours (Jordan, et al. 2007), and there is evidence from epidemiological, histopathological and molecular studies that these borderline tumours may develop from benign tumours in a neoplastic progression (Jordan, et al 2006). Our finding that low grade but not high grade invasive serous tumours were also associated with BMI supports this theory of progression for low grade serous cancers.…”

Section: Discussionmentioning

confidence: 99%

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Olsen

Nagle

Whiteman

et al. 2013

Endocrine-Related Cancer

192

138

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Whilst previous studies have reported that higher body-mass index (BMI) increases a woman’s risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum, and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13,548 cases, 17,913 controls). We combined study-specific adjusted odds ratios (ORs) using a random–effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5kg/m2; 95%CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post–menopausal women, the associations did not differ between HRT users and non–users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

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“…It has been hypothesized that both serous low grade and mucinous low grade tumors develop in a stepwise manner from well-recognized precursors, namely borderline tumors that may in turn develop from cystadenomas and adenofibromas [136, 137]. Molecular evidence that supports this hypothesis is the identification ofthe same KRAS mutation in benign, borderline and malignant portions of the same tumor [132, 133, 138] and the gradual increase in chromosome instability observed in benign, borderline and malignant tumors [53].…”

Section: Molecular Pathogenesis Of Ovarian Cancermentioning

confidence: 99%

“…Molecular evidence that supports this hypothesis is the identification ofthe same KRAS mutation in benign, borderline and malignant portions of the same tumor [132, 133, 138] and the gradual increase in chromosome instability observed in benign, borderline and malignant tumors [53]. The majority of benign epithelial ovarian tumors are of the serous and mucinous subtype [136] and it is generally accepted that the ovarian surface epithelium or its Mullerian inclusion cysts are a common site for the initiation of serous low grade and mucinous ovarian carcinogenesis [53, 139]. …”

Section: Molecular Pathogenesis Of Ovarian Cancermentioning

confidence: 99%

Molecular pathogenesis of endometrial and ovarian cancer

Merritt

Cramer

2011

CBM

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Pregnancy, breastfeeding, and oral contraceptive pill use interrupt menstrual cycles and reduce endometrial and ovarian cancer risk. This suggests the importance of turnover within Mullerian tissues, where the accumulation of mutations in p53 and PTEN has been correlated with number of cycles. The most common type of endometrial cancer (Type I) is endometrioid and molecular abnormalities include mutations in PTEN, KRAS and β-catenin. The Type I precursor is Endometrial lntraepithelial Neoplasia which displays PTEN defects. Type II endometrial cancer (whose precursors are less clear) includes serous and clear cell tumors and the most common alteration is p53 mutation. For ovarian cancer, histopathologic types parallel endometrial cancer and include serous, mucinous, endometrioid, and clear cell; some molecular features are also shared. The most frequent type of ovarian cancer is high grade serous that often displays p53 mutation and its precursor lesions may originate from normal-appearing fallopian tube epithelium that contains a p53 “signature”. Mutations in KRAS, BRAF and PTEN are described in mucinous, endometrioid and low grade serous cancers and these may originate from ovarian cortical inclusion cysts. A consideration of molecular and other pathogenetic features, like epidemiology and histopathology, may provide a bener understanding of endometrial and ovarian cancer.

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Benign Epithelial Ovarian Tumours—cancer Precursors or Markers for Ovarian Cancer Risk?

Cited by 27 publications

References 60 publications

Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Molecular pathogenesis of endometrial and ovarian cancer

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