Association of Estrogen Receptor TA Repeats with Endometrial and Ovarian Cancers in Basrah Province

BackgroundThe relationship between statin use and the risk of ovarian or endometrial cancer remains controversial. Here, we investigated the relationship between statin use and the risk of ovarian and endometrial cancers.MethodsWe conducted a meta-analysis using articles retrieved from the PubMed, Embase, and Web of Science databases. All original comparative studies published in English that were related to statin use and the risk of ovarian or endometrial cancer were included.ResultsThis meta-analysis included 19 studies enrolling 1,999,362 female subjects and 19,849 cancer cases (7,948 ovarian cancer cases and 11,901 endometrial cancer cases). The overall analysis indicated that statin use did not significantly reduce the risk of ovarian cancer [relative risk (RR) = 0.88, 95% confidence interval (CI) 0.76–1.03, p = 0.12] or the risk of endometrial cancer (RR = 0.88, 95% CI 0.78–1.00, p = 0.05.) Subgroup analyses based on study type, percentage of cancer cases, study location, and quality of studies also supported our conclusions. No association was found between long-term statin use (> 5 years) and the risk of ovarian cancer (RR = 0.73, 95% CI 0.51–1.04, p = 0.08) or endometrial cancer (RR = 0.79, 95% CI 0.58–1.08, p = 0.14).ConclusionsStatin use did not lower the risk of ovarian cancer or endometrial cancer. The long-term use of statins (> 5 years) was not associated with a reduction in the risk of ovarian or endometrial cancer.

Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiologic studies on acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk for breast, endometrial, and ovarian cancers in a prospective cohort study. We assessed acrylamide intake among 88,672 women in the Nurses' Health Study using food frequency questionnaires administered every 4 years. Between 1980 and 2006, we identified 6,301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk. We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk for endometrial cancer among high acrylamide consumers (adjusted relative risk for highest versus lowest quintile = 1.41; 95% CI, 1.01-1.97; P for trend = 0.03). We observed a nonsignificant suggestion of increased risk for ovarian cancer overall (relative risk, 1.25; 95% CI, 0.88-1.77; P trend = 0.12), with a significantly increased risk for serous tumors (relative risk, 1.58; 95% CI, 0.99-2.52; P trend = 0.04). Associations did not differ by smoking status. We observed no association between acrylamide and breast cancer. Risk for endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers. This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy.

Ovarian cancer typically presents late and has a poor prognosis. Ovarian screening aims to reduce mortality from the disease by detecting and treating women at an earlier, presymptomatic stage. The paper by Menon et al.1 published in BJOG more than a decade ago, set the stage for a multimodal approach to ovarian cancer screening, whereby a combination of CA125 levels and ultrasound scan findings could identify women at risk of the disease. Subsequent studies have not only informed the current management of women with suspected ovarian cancer but will also determine whether ovarian cancer screening can save lives. This commentary documents the ovarian screening story so far from inception to current day as we await the results from UKCTOCS, the largest ovarian cancer screening trial conducted to date. Ovarian cancer is known as the ‘silent killer’ because it only becomes symptomatic in its late stages. Compared with other common cancers, women diagnosed with ovarian cancer have a relatively poor prognosis. The overall 5-year survival rate of 42.9% masks vast differences in prognosis for those women presenting with Stage I disease compared with those with Stage IV disease.2 Since the late 1980s there has been a steady improvement in 5-year survival in the relatively small group of women who present with Stage I disease from 80% in 1987–91 to 92% in 2005–08.3 Changes in survival for the much larger proportion of women who present with Stage III and IV disease have been more modest. The 5-year survival rate for those with stage IV disease, however, stands unchanged at around 5%.3 These dismal survival rates for most women with ovarian cancer have stimulated enormous research effort aimed at identifying and treating women with early-stage disease. The hypothesis is that ovarian cancer screening may pick up early, asymptomatic disease in apparently healthy women that is then more amenable to surgical cure than disease that presents with symptoms. A major challenge when screening an asymptomatic population is that the proportion of true positives is extremely low given that the age-standardised incidence of ovarian cancer is only 16 per 100 000.4 Furthermore, the consequence of a positive screen is referral for laparoscopy/laparotomy with its incumbent risks. Hence, it has been suggested to ensure an acceptable false-positive rate any test needs to achieve a specificity of over 99.6%.5 This equates to nine women being offered further investigation or treatment for every woman diagnosed with an ovarian malignancy. This degree of specificity has not been achieved by any individual marker alone. To overcome this obstacle a number of strategies incorporating multiple markers have been proposed since the 1980s. The CA125 antigen was discovered in the early 1980s as part of an effort to develop a monoclonal antibody that could be used for immunotherapy of ovarian cancer.6 In this regard CA125 appeared to be relatively specific to epithelial ovarian cancers, being expressed in up to 80% of these cancers. Furthermore, it was found in the serum of women with ovarian cancer, although it can also be raised in a number of other cancers as well as some benign conditions. Although targeting CA125 has not proved to be therapeutically successful,7, 8 it was to prove a much more useful diagnostic/predictive biomarker. Its promise as a marker of early disease was shown in studies led by Zurawski in the 1980s. Serum CA125 levels were rarely elevated in healthy postmenopausal women9 but in up to 20% of cases, raised CA125 could be seen at least 2 years before ovarian cancer diagnosis.10 Alone, a raised CA125 has a high specificity but the likelihood of a woman having an occult cancer with a raised CA125 (Positive Predictive Value; PPV) remains low. PPV and sensitivity are determined in large part by the cut-offs used. Early studies by Klug et al. had determined that if a cut-off of 35 U/ml was used, then 82% of women with cancer, 6% of women with benign disease and 1% of normal women would have a raised CA125. Increasing the cut-off to 65 U/ml saw the percentage of ovarian cancer patients with a positive CA125 fall to 73% but those with benign disease and normal disease drop to 2% and 1%, respectively. To ensure that no women with benign disease would be included would necessitate the reference value to be set at 220 U/ml, which would mean that nearly 40% of women with ovarian cancers would be missed. Clearly serum CA125 measurement as a sole test was unlikely to offer the assurance of a low false-positive and false-negative rate needed to roll-out population screening. The 1950s saw the development of medical ultrasound and with it the ability to characterise gynaecological masses. Fittingly it was one of the first uses demonstrated by the seminal work of Ian Donald, Professor of Midwifery and a pioneer of diagnostic ultrasound.11 However, it would not be until the 1970s that this diagnostic tool was perceived to be a viable method for early detection in its own right, rather than a simple adjunct to the clinical examination of the symptomatic woman. Advances in ultrasound technology meant that by the mid-1970s lesions of 1 cm in diameter, which would normally be undetectable clinically, could be defined by ultrasound.12 Furthermore, various criteria to distinguish benign from malignant lesions with accuracies ranging from 70 to 90% were proposed.13-15 In 1982, Campbell et al.16 suggested that because ultrasound was able to define ovarian size accurately, ovarian volume could be a useful discriminator for potential ovarian disease in postmenopausal women. This strategy was studied in a large-scale prospective study of 5479 women followed over 8 years.17 Campbell et al. were able to identify 100% of the women that developed primary ovarian cancer within this time frame. The specificity of this procedure was 97.1% with a PPV of 1.5%, i.e. odds of a positive screen result representing a primary cancer of 1 in 67. Although Campbell et al. were able to demonstrate the utility of transabdominal ultrasound to identify women with asymptomatic ovarian masses, the inability to satisfactorily distinguish those with benign from malignant lesions underlies the high false-positive rates. The first approach proposed to reduce false positives was that only women with increasing ovarian volumes at a second scan, who had previously demonstrated either ovarian volumes >96th centile or abnormal morphology, e.g. cystic areas, should be offered surgery.18 Under this strategy, the PPV rose to 2.0%. The second approach came with the advent of transvaginal and Doppler ultrasound. Transvaginal ultrasound provided a higher resolution and so had the ability to detect abnormal morphology in smaller ovaries, while Doppler ultrasound provided the ability to visualise areas of neovascularisation more common in malignant lesions. Small studies showed promising results for the detection of women with ovarian pathology and the distinction of benign from malignant disease using transvaginal ultrasonography.19 The University of Kentucky Ovarian Cancer Screening Project was the first large-scale prospective trial to investigate whether transvaginal ultrasound assessment of ovarian volume could be used in ovarian cancer screening in pre- and postmenopausal women. In total, 90 women (1.4%) with persistent abnormalities were offered surgery to remove the affected ovary; six of whom were discovered to have a primary ovarian cancer. Overall, this strategy resulted in a sensitivity of 85.7%, specificity of 98.7% and 14 false positives for every woman with screen-detected ovarian cancer. Forgoing the possibility that the removal of benign ovarian masses with the potential for malignant transformation may lead to a resultant late fall in mortality from ovarian cancer, there remained a need for strategies to reduce the proportion of false positives. Jacobs et al.5 were the first to describe a multimodal approach for ovarian cancer screening in 1988. In their initial study, 1010 healthy postmenopausal women were offered serum CA125 measurement and a clinical pelvic examination. If either the clinical or biochemical assessment was abnormal women were offered a transabdominal ultrasound scan to assess ovarian volume. When CA125 measurements were considered individually, specificity was 97%, but when ultrasonography was added as a secondary test, specificity increased to 99.8%. This two-stage strategy was validated by a larger prevalence study in which 22 000 women were screened. With this approach equally high specificity and PPVs were achieved for a sensitivity of 79% at 1 year of follow up when a cut-off of 30 U/ml was used.20 The same cohort was then randomised to annual incidence screening or no further screening and followed up over 8 years. Initially, women recruited to this study in the late 1980s were offered transabdominal ultrasonography on entry. Subsequently, as evidence of the superiority of the transvaginal route in terms of image resolution with high acceptability among patients became available, follow-up scans were offered transvaginally. In contrast to the Kentucky Ovarian Cancer Screening Project, only postmenopausal women who had an abnormal CA125 were offered an ultrasound. In this preselected group of women, ultrasonographical assessment led to a much higher PPV of 21.3% and 23.75%, respectively, when ovarian volume and morphology were considered separately.1 Furthermore, there appeared to be minimal loss in sensitivity or specificity with this approach (sensitivity 89.5% and 100%; specificity 93.75% and 93.95% when considering ovarian volume and morphology, respectively). This was a breakthrough as it demonstrated that the target of nine healthy women being investigated or treated for every woman with cancer identified by screening was not only attainable but could be improved upon. This landmark finding stimulated a new wave of research to refine the detection of early ovarian cancers by screening. While early detection is fundamental, it is only relevant if it can translate into lives saved. Further analysis showed that screening identified proportionately more early-stage ovarian cancer (31.3% versus 10%), although the difference between the two groups was not statistically significant (P = 0.171).21 Nevertheless, the histological grade was lower and length of survival following randomisation was longer for women with ovarian cancer in the screened group (P = 0.02 and P = 0.01, respectively). Despite large numbers, the study was underpowered to detect a difference in mortality among screened and unscreened women, setting the scene for a still larger trial to answer this crucial question. Until 1998 there had been 25 prospective studies of ovarian cancer screening but no comparison with an unscreened population.22 Both ultrasound-based and multimodal screening strategies appeared to be able to identify asymptomatic women with ovarian cancer at early stages, but the clinical significance of this in terms of survival and mortality remained unknown. Furthermore ultrasound-based techniques appeared to offer higher sensitivity although at the cost of lower specificity, than multimodal screening. Notably, most of the women who received diagnostic surgery as a result, were found to have a benign gynaecological condition. Again the clinical impact of surgery in these circumstances is unclear. To answer this question UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening), the largest randomised control trial to date of an ovarian cancer screening strategy, involving over 200 000 women followed over 7 years was established. This study primarily aimed to ascertain whether screening, be it by a multimodal or imaging-only approach, could have an impact on ovarian cancer mortality. The trial would also assess the physical and psychological impact of screening, volunteer compliance and cost-effectiveness to inform decisions about the use of a national screening programme. As a result of further analysis of data from the pilot study, the multimodal arm had a new weapon in its armamentarium: the Risk of Ovarian Cancer algorithm (ROCA).23 This algorithm stratifies patients according to their CA125 trajectory rather than using a single threshold of 30 U/ml and is recalculated with every successive CA125 result. It was designed to improve sensitivity for the detection of early-stage cancers where earlier intervention could offer the most survival benefit and where CA125 is >30 U/ml in only 57% of cases, compared with 84% of late-stage cancers.24 Using the ROCA, a woman with a low baseline CA125 that suddenly rose would be identified as at risk of ovarian cancer, even if the absolute level remained modest, while a woman with a static but high CA125 would be deemed low risk. Retrospective testing of the algorithm on a Swedish cohort demonstrated high levels of sensitivity and specificity, which were subsequently verified by a prospective cohort of over 16 000 women between 1995 and 2000.25-27 More recently, ROCA was employed by Lu et al.28 in a large single-arm prospective study, which like UKCTOCS triaged women deemed high risk by ROCA to transvaginal ultrasound. Encouragingly, this protocol resulted in <1% of women being referred for surgery, giving it a specificity of 99.9% (95% confidence interval 99.7–100%) and a PPV of 40% (95% confidence interval of 12.2–78%).28 This equates to just over two women requiring surgery for every woman diagnosed with cancer. The pilot study published in BJOG,1 although primarily aimed at providing the platform for general population screening for postmenopausal women in whom 90% of ovarian cancer occurs, also provided the basis for studies in a second group of women with a family history of ovarian cancer. Some women are diagnosed with gene faults that increase their risk of ovarian and also breast cancer, notably defects in the BRCA1 and BRCA2 genes, but others have unidentified gene faults and/or are labelled as ‘at risk’ by virtue of their strong family history. Given the poor prognosis of ovarian cancer presenting symptomatically, women at high risk of ovarian cancer are currently offered risk-reducing prophylactic salpingo-oophorectomy (RRSO) to prevent incident ovarian cancers and reduce their risk of premenopausal breast cancer. When performed in young women, such surgery inevitably results in infertility and premature menopause and so screening may facilitate women safely delaying surgery until after their natural menopause. The United Kingdom Familial Ovarian Cancer Screening Study (UKFOCSS) recruited 3563 women with a 10% or greater lifetime risk of ovarian cancer between 2002 and 2008 to determine whether screening could be a viable alternative to RRSO. Reports from the first phase of the UKFOCSS study suggest that a negative screen can reliably reassure women (99.9% probability) that they will not develop ovarian cancer in the subsequent year. Screening was able to detect incident disease with a sensitivity of >80% and may reduce the proportion of stage IIIc disease.29 Phase II of the study drew on the successes of the UKCTOCS by stratifying patients according to ROCA using a computerised system, which would prompt investigators to repeat blood tests in women with intermediate risk and organise scans/referrals in women who were high risk. Additionally, screening intervals were reduced to 4 months to reduce false negatives.29 These amendments to the study design resulted in no interval cancers in this phase with no significant increase in the proportion of women referred.30 PPV in this phase was 13%. All women diagnosed with ovarian cancer as a result of screening went on to have optimal cytoreduction at surgery and survival was increased by 43 months.30 However, until such time as the efficacy of screening in this context has been fully evaluated, RRSO will remain the recommended intervention in women with a genetic predisposition to ovarian cancer. This research1 has also benefitted women with suspected ovarian cancer. The search for screening strategies which could be translated from women with clinically apparent cysts to those with occult disease fortuitously led to the development of the ‘Risk of Malignancy’ Index (RMI).31 This simple algorithm combines three factors that are independently predictive for an increased risk of ovarian cancer; menopausal status (scored 1or 3), serum CA125 and ultrasound features of the cyst (scored 0, 1 or 3). The product of these three criteria results in a score that can be used to provide a quantitative and reproducible assessment of likelihood that a symptomatic patient does indeed have an ovarian malignancy. Cut-offs can be useful tools for clinical decision making, e.g. referral to tertiary gynaecological oncology centres for surgery. To put this into context an RMI of 200 equates to a likelihood ratio of 42.1 of malignant disease and a likelihood ratio of 0.22 of benign disease; a 280-fold difference.32 Although the effect of the use of the RMI on the prognosis of a woman diagnosed with ovarian cancer has not been formally assessed, many studies have demonstrated the survival benefit of being treated by a specialist gynaecological oncologist.33 Where resources are limited, adjusting cut-offs can ensure only those at highest risk will be referred to tertiary centres. RMI remains the most widely used and evidenced stratification tool34 and in the UK, National Institute for Health and Care Excellence (NICE) guidance suggests the use of this tool to assess all women presenting to primary and secondary care with suspected ovarian cancer. The beauty of the RMI is its simplicity, which has helped it to stand the test of time. Accurate ultrasound assessment of an adnexal mass is fundamental to the success of the RMI. Substituting the subjective assessment by a skilled sonographer35-37 with a score defined by the presence or absence of certain key features facilitates reproducibility. However, the diagnostic test accuracy of the RMI appears lower in external validation studies than the original publications.38, 39 The International Ovarian Tumour Analysis (IOTA) collaboration was formed to encourage the development of better indices by standardising ultrasound reporting across research groups and prospectively collecting a database of features observed in cancerous and benign cysts from which new models could be developed and validated. Initial reports suggest that IOTA models (including simple rules and LR2) demonstrate better sensitivity for the detection of ovarian cancer with a lower false-positive rate than the RMI.38, 40 The challenge is to demonstrate the translation of highly sophisticated ultrasound protocols into ‘real-life’ clinical practice in different centres around the world.41 Women's symptoms have also gained attention as the search for strategies to reduce mortality from ovarian cancer through early detection has gathered pace. To this end, Goff et al.42 developed a symptom index using questionnaire data from women with and without ovarian cancer who were participating in a screening study. Over two-thirds of women had symptoms between 3 and 36 months before diagnosis. Using the Goff index the sensitivity for ovarian disease is 66.7% for a specificity of 90%, which has been validated in a number of external studies.43-45 This has formed the basis of the recommendation in the UK by NICE that symptomatic women are identified as at risk of ovarian cancer and offered further assessment. Much of the criticism surrounding general population screening for ovarian cancer is that low PPV would lead to the overtreatment of large numbers of women. A recent study has demonstrated that the prevalence of ovarian cancer among symptomatic women is ten times higher than that seen in asymptomatic women.46 Furthermore, when offered assessment with CA125 and transvaginal ultrasound at presentation, symptomatic women had lower tumour burdens, which were then more amenable to complete surgical resection, though unfortunately not earlier stage disease than those presenting to gynaecological oncologists by traditional routes. It is suggested that detecting women with lower tumour burdens may account for the increased survival of women diagnosed with stage 3 disease in the first randomised control trials of ovarian cancer screening.47 Data from UKCTOCS showed that the risk of a woman with an adnexal mass developing ovarian cancer within 3 years is 1 in 22.48 Therefore screening asymptomatic women for ovarian cancer will no doubt increase the numbers of women with incidental findings. On the one hand this has offered an unprecedented opportunity to conduct a number of nested cohort studies to assess the natural history of the conditions readily detectable by ultrasonography. But on the other hand, incidental findings cause and will resources in terms of and/or surgery. The of cancers which would not have clinically is a in The incidental finding of cancer is Although has been widely as a risk for cancer in women with postmenopausal the significance of a in the asymptomatic and so its potential use as a screening tool for cancer, is from UKCTOCS suggest that the cut-off for the detection of women with asymptomatic cancer or needs to be in the of as to the used cut-off of in symptomatic But even with an of the risk of cancer in an asymptomatic woman remains low at just Further studies will be needed to the value of early detection of cancer, the acceptability of screening and In the of the roll-out of an ovarian cancer screening that pelvic the need for such studies will more saw a to the cause of ovarian cancer screening. The and Ovarian Cancer Screening which randomised women to ovarian cancer screening, that there was no overall mortality benefit for annual with CA125 and transvaginal ultrasound rate confidence interval Furthermore there was no difference in survival or stage at between the screened and unscreened Additionally, this intervention resulted in more women to from to potential ovarian cancer. in study design between and UKCTOCS provide the that screening may offer for women with ovarian cancer. of the protocol that the study used a single cut-off CA125 level rather than the ROCA to identify women at had clinical in to with positive and follow up for many years after the screening were which time they to Initial data from UKCTOCS have been with of the ovarian cancers identified being as providing evidence for a in screened have suggested that these strategies identify and I cancers which may have clinically apparent within a II cancers representing up to of ovarian cancers diagnosed in symptomatic women, over two-thirds of the ovarian cancers identified by ultrasonography in UKCTOCS were or I screening appears to be more specific for II cancers but screening have had a number of interval cancers all of which were II cancers. These findings are in with the current that ovarian cancers may in the rather than from ovarian the women diagnosed with II cancers, had no adnexal pathology and were diagnosed at an It has been suggested that differences in the that CA125 was used to determine screen in the two trials for the of sensitivity of the trial to detect early Although of the algorithm to the data to any data from the Risk Ovarian Screening Study where women from the general population were using the ROCA followed by transvaginal ultrasound scan if they as high showed specificity and high PPV for the detection of ovarian It is that the UKCTOCS trial will answer whether CA125 as a test will be to translate to in ovarian cancer mortality. If UKCTOCS does not demonstrate survival or mortality benefit from general population ovarian cancer screening, it is to that any randomised trials will be to this given the to such a study The of any benefit from ovarian cancer screening in may be by poor sensitivity of screening to detect true early disease. disease suggests that cancers 90% of the of opportunity where intervention may prognosis at and may have been present for between 8 and years before detectable by current CA125 current screening strategies may detect disease at a that is late to disease The prospective of serum in asymptomatic women may result in the of more relevant of early disease than have been suggested by the comparison of from women with clinically detectable cancers with studies aimed at identifying an from the serum of women who subsequently developed ovarian cancer in UKCTOCS are The years have seen a in the of ovarian cancer, its natural history and the of mortality. Despite in and there has been in the prognosis for women with disease. with the ability of ovarian cancer screening strategies to the of disease to earlier stages, which may translate to better clinical and reduced mortality. screening and ultrasound-based have been shown to be and specific for detecting ovarian cancer but whether these in will provide lead time to the of the disease remains to be success will on the of the multiple and to ensure that research will for better that can be translated into clinical It is that and to the and on the by the high compliance rates seen in the screening studies to work mortality from ovarian cancer. have no to and this was to this is a and is an at the Institute of Cancer University of

Ultraprocessed food intake and risk of ovarian and endometrial cancer in the NIH-AARP cohort: a prospective cohort analysis.

Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism. Hormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT). Women using exogenous hormones at baseline (1992-1993) were excluded. Incident endometrial (n = 65) and ovarian (n = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk. Circulating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85-4.11); P trend = 0.17] or ovarian cancer risk [1.16 (0.58-2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09-0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18-0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39-6.93); 0.01]. Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer. While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder in women that may be associated with an increased risk of various cancers. This meta-analysis aims to evaluate the relationship between PCOS and the risk of breast, ovarian, and endometrial cancers. We performed a comprehensive search of databases, including PubMed (Medline), Scopus, Web of Science, and Embase (Elsevier), covering the period from 1983 to November 2023. The review included cohort studies (both retrospective and prospective) and case-control studies. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Data analysis was conducted with Stata 17. Our meta-analysis reviewed 13 studies on the association between Polycystic Ovary Syndrome (PCOS) and endometrial cancer, revealing a combined Relative Risk (RR) of 2.91 (95% CI: 2.29 - 3.70; I²: 61.97%; P < 0.001), indicating a significantly increased risk of endometrial cancer among women with PCOS. For breast cancer, the pooled RR from the studies was 1.09 (95% CI: 0.97-1.22; I²: 55.81%; P = 0.012), suggesting a modestly elevated risk. In the case of ovarian cancer, seven studies contributed to the analysis, resulting in a combined RR of 1.52 (95% CI: 1.17-1.97; I²: 49.22%; P = 0.072). This finding indicates a moderate increase in risk for ovarian cancer in women with PCOS. These results collectively point to an elevated risk of endometrial, breast, and ovarian cancers in women with PCOS, although the magnitude of risk varies among different types of cancer. This meta-analysis supports an elevated risk of endometrial, breast, and ovarian cancers in women with PCOS. These findings highlight the need for increased surveillance and preventive measures for women with PCOS to mitigate their cancer risk. Further research with larger sample sizes is needed to confirm these associations and explore underlying mechanisms.

Sugar-containing beverages and their association with risk of breast, endometrial, ovarian and colorectal cancers among Canadian women

OBJECTIVE--To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN--Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING--Iceland. SUBJECTS--The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES--Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS--The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS--Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.

To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. Iceland. The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.

Background: Obesity is related to major risk factors for a number of noncommunicable diseases including cancer. There is a high incidence of breast and endometrial cancer in obese women. Thus, we performed a systematic review followed by meta-analysis to evaluate the relationship between bariatric surgery, a method widely used to treat obesity, and the risk of developing breast, ovarian and endometrial cancer in obese women. Methods: MEDLINE, EMBASE, LILACS and Cochrane databases were searched from inception until January 2019 which retrieve studies to assessed the risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery. There was no language restriction. We extracted and combined data from studies in order to assess the risk ratio (RR) of developing these cancers. A random-effects, meta-analytic model was applied in all calculations. The New Castle Ottawa and GRADE were used to assess quality and bias of the included studies. Trial registered in PROSPERO (CRD42019112927). Results: We found 188 articles and only seven of those were included in our meta-analysis, which incorporated a total of 150,528 patients in the bariatric surgery arm and 1,461,938 women in the control arm. The total risk of developing breast, ovarian and endometrial cancer was 0.37 (95%CI [0.28 to 0.48]; I2=87%; 7 studies). The risk of breast cancer was reduced by 61% [RR: 0.39 (95%CI [0.24 to 0.64]; I2= 90%; 6 studies). The risk of ovarian cancer was reduced by 53% [RR: 0.47 (95%CI [0.27 to 0.81]; I2= 0%; 3 studies). The risk of endometrial cancer was reduced by 67% [RR: 0.33 (95%CI [0.21 to 0.51]; I2= 88%; 7 studies). Conclusion: Bariatric surgery may have a protective effect by reducing the risk of developing breast, ovarian and endometrial cancer in obese women. However, high heterogeneity was found and not explained by our subgroup analysis. Although we couldn’t separate the types of surgeries performed, we hypothesized that the high heterogeneity might be due to the types of surgery. Therefore, we suggest more research with appropriate report of the type of the surgery by group. Citation Format: Beatriz Pércia Ishihara, Daniela Farah, Marcelo Cunio Machado Fonseca, Afonso Celso Pinto Nazário. The risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-19.

Levonorgestrel-releasing intrauterine system use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer. Results from the NOWAC Study

BackgroundSurgery is a cornerstone in management of ovarian and endometrial cancer. The European Society of Gynecological Oncology introduced quality indicators to improve management of these cancers. The optimal annual number of surgeries per unit was established for high-quality surgical treatment.Material/MethodsThe database of the National Health Fund on surgical management of endometrial and ovarian cancer was analyzed. Patients treated between 2017 and 2020 were included. Departments where patients underwent surgery were divided according to number of surgeries performed per year in endometrial cancer: ≥80, 79-50, 49-20, 19-0; and ovarian cancer: ≥100, 99-50, 49-20, 19-0. Optimal number of surgeries per center was defined as at least 100 and 80 surgeries per year in ovarian and endometrial cancer, respectively.ResultsTotally, there were 22 325 surgeries in 316 units and 10 381 surgeries in 251 units due to endometrial and ovarian cancer, respectively. Most surgeries in endometrial cancer (n=15 077; 67.5%) and ovarian cancer (n=9642; 92.88%) were performed in departments that did not meet optimal criteria in number of surgeries. Between 2017 and 2019, an increasing trend in number of surgeries per year in endometrial and ovarian cancer was found. In 2020, there was a decrease in the number of surgeries by 7.8% (n=453) and 8.6% (n=234) in endometrial and ovarian cancer, respectively.ConclusionsIn Poland, surgical treatment of ovarian and endometrial cancer is decentralized. Most cancer patients underwent surgery in low-volume general gynecologic departments. The COVID-19 pandemic impaired cancer management, leading to a decreased number of surgeries.

Women with Lynch syndrome have an additional need to address the substantial increased lifetime risk of endometrial and ovarian cancer. Endometrial or ovarian cancer can be the presenting cancer in individuals with Lynch syndrome, or can be a second cancer. Lifetime risk of endometrial cancer in women with MLH1 or MSH2 mutations is approximately 40%, with a median age of 49. Women with MSH6 mutations have a similar risk of endometrial cancer but a later age of diagnosis. Lynch syndrome-associated endometrial cancers are primarily endometrioid, although non-endometrioid subtypes including clear cell, papillary serous and MMMT have been reported. In addition, endometrial cancers arising in the lower uterine segment, while rare in the general population, are enriched in women with Lynch syndrome. Ovarian cancer risk in women with Lynch syndrome is 6-8%, and Lynch syndrome-associated ovarian cancers exhibit a variety of histopathological subtypes. Studies of endometrial cancer screening in Lynch syndrome have been small, and more recently have focused on the use of office endometrial biopsy to identify pre-malignant and early stage cancers. Prevention options include the use of oral contraceptives, which are known to be highly effective for decreasing risk of both endometrial and ovarian cancer in the general population, and prophylactic surgery to remove the uterus and ovaries.

An analysis of the association between statin use and risk of endometrial and ovarian cancers in the Women's Health Initiative

The effect of bisphosphonates on the risk of endometrial and ovarian malignancies