Risk Factors For Ovarian Cancer Research Articles

Tubal ligation during cesarean delivery and future risk for ovarian cancer: a population-based cohort study.

Data regarding the effect of post-partum bilateral tubal ligation (BTL) on future risk for ovarian cancer (OC) is lacking. In the current study, we aimed to evaluate the effect of BTL during cesarean delivery (CD) on the long-term risk for OC. A population-based cohort analysis of women above the age of 35 that underwent CD in their last delivery, comparing the long-term risk for OC between patients that had a Pomeroy excisional BTL and those that did not. OC diagnosis was pre-defined based on ICD-9 codes. Procedures occurred between the years 1991-2017. Kaplan-Meier survival curve was used to compare the cumulative incidence of OC over time and Cox proportional hazards model was constructed to control for confounders. During the study period 13,124 women met the inclusion criteria; 9438 (71.9%) of which had only CD and 3686 (28.1%) underwent CD with BTL. Despite the significantly higher incidence of maternal factors that might increase the long-term risk for OC in the BTL group (advanced maternal age, obesity, hypertensive diseases during pregnancy and diabetes mellitus), the cumulative incidence of OC cases was not significantly different between the two groups (Log-rank test p = 0.199). Likewise, when performing a Cox regression model controlling for maternal age, obesity, hypertensive diseases and diabetes, OC risk was not significantly different between the groups (adjusted HR 2.36, 95% CI 0.73-7.62; p = 0.149). Despite an increased incidence of known risk factors for OC, patients that underwent BTL during CD did not have increased long-term risk for OC.

A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk.

Ovarian cancer has few known risk factors, hampering identification of high-risk women. We assessed the association of prediagnostic plasma metabolites (N = 420) with risk of epithelial ovarian cancer, including both borderline and invasive tumors. A total of 252 cases and 252 matched controls from the Nurses' Health Studies were included. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI), comparing the 90th-10th percentile in metabolite levels, using the permutation-based Westfall and Young approach to account for testing multiple correlated hypotheses. Weighted gene coexpression network analysis (WGCNA; n = 10 metabolite modules) and metabolite set enrichment analysis (n = 23 metabolite classes) were also evaluated. An increase in pseudouridine levels from the 10th to the 90th percentile was associated with a 2.5-fold increased risk of overall ovarian cancer (OR = 2.56; 95% CI, 1.48-4.45; P = 0.001/adjusted P = 0.15); a similar risk estimate was observed for serous/poorly differentiated tumors (n = 176 cases; comparable OR = 2.38; 95% CI, 1.33-4.32; P = 0.004/adjusted P = 0.55). For nonserous tumors (n = 34 cases), pseudouridine and C36:2 phosphatidylcholine plasmalogen had the strongest statistical associations (OR = 9.84; 95% CI, 2.89-37.82; P < 0.001/adjusted P = 0.07; and OR = 0.11; 95% CI, 0.03-0.35; P < 0.001/adjusted P = 0.06, respectively). Five WGCNA modules and 9 classes were associated with risk overall at FDR ≤ 0.20. Triacylglycerols (TAG) showed heterogeneity by tumor aggressiveness (case-only heterogeneity P < 0.0001). The TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. In summary, this study suggests that pseudouridine may be a novel risk factor for ovarian cancer and that TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features. SIGNIFICANCE: Pseudouridine represents a potential novel risk factor for ovarian cancer and triglycerides may be important particularly in rapidly fatal ovarian tumors.

Metformin Abrogates Age-Associated Ovarian Fibrosis.

The ovarian cancer risk factors of age and ovulation are curious because ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased. To determine how age and ovulation underlie ovarian cancer risk, we assessed the effects of these risk factors on the ovarian microenvironment. Aged C57/lcrfa mice (0-33 months old) were generated to assess the aged ovarian microenvironment. To expand our findings into human aging, we assembled a cohort of normal human ovaries (n = 18, 21-71 years old). To validate our findings, an independent cohort of normal human ovaries was assembled (n = 9, 41-82 years old). We first validated the presence of age-associated murine ovarian fibrosis. Using interdisciplinary methodologies, we provide novel evidence that ovarian fibrosis also develops in human postmenopausal ovaries across two independent cohorts (n = 27). Fibrotic ovaries have an increased CD206+:CD68+ cell ratio, CD8+ T-cell infiltration, and profibrotic DPP4+αSMA+ fibroblasts. Metformin use was associated with attenuated CD8+ T-cell infiltration and reduced CD206+:CD68+ cell ratio. These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis.See related commentary by Madariaga et al., p. 523.

Predictors of female health care providers' knowledge on symptoms and risk factors of ovarian cancer: A tertiary health care institutional based cross-sectional study

Context: Ovarian cancer is responsible for more deaths per year than all other gynaecological cancers combined, and its overall mortality is high because of late presentation. Aims: To evaluate the predictors of knowledge of the symptoms and the risk factors of ovarian cancer among female healthcare providers in Enugu, Nigeria. Settings and Design: Cross-sectional survey conducted at the University of Nigeria Teaching Hospital (UNTH), Enugu from June to August 2018. Subjects and Methods: A self-administered, structured questionnaire on symptoms and risk factors of ovarian cancer was given to 422 randomly selected female healthcare providers working at UNTH. Statistical Analysis: Data were analysed using SPSS version 22.0 for Windows (Chicago, IL, USA). Predictors of knowledge level were determined using logistic regression. P

Risk Factors of Ovarian Cancer in PKU Muhammadiyah Teaching Hospital Yogyakarta

In t roduction: Ovarian cancer is non-communicable diseases that has a high mortality rate. In PKU Muhammadiyah Teaching Hospital Yogyakarta in 2014-2017, ovarian cancer is 5 th out of all types cancers diagnosed. Most of them are asymptomatic in early stage and come to hospital at late stage. Recognize and identify the risk factors of ovarian cancer are very important to prevent the patient from morbidity and mortality. The purpose of this study was to know the relationship between low parity, infertility, age, and family history with ovarian cancer in PKU Muhammadiyah Teaching Hospital Yogyakarta. Methods: This study was an observational analytical study with cross sectional design. The sample was medical record of women with ovarian cancer and non ovarian cancer in PKU Muhammadiyah Teaching Hospital Yogyakarta period of April 2014-September 2017 with inclusion and exclusion criteria. Data analysis used chi-square test. Result: The bivariat analysis showed that there is no relationship between low parity with ovarian cancer (p=0,790 OR=0,87; 95% CI 0,305-2,466), there is no relation between infertility with ovarian cancer (p=0,104 OR=2,48; 95% CI 0,815-7,545), and there is no relation between family history with ovarian cancer (p=0,304 OR=3,18; 95% CI 0,315-32,039). But there is a relationship between age with ovarian cancer (p=0,01 OR=0,11; 95% CI 0,022-0,510). Conclusion: There are no relations between low parity, infertility, and family history with ovarian cancer. But there is a relationship between age with ovarian cancer.

Risk factors for ovarian cancer in Yaounde: A case control study

Risk factors for ovarian cancer in Yaounde: A case control study

A cross-sectional study of ovarian cancer knowledge and its determinants among females

Background: Ovarian cancer has the highest mortality rate among all gynecological cancers. However, early detection of the disease could improve patients' outcomes. This could be achieved by satisfying knowledge about the risk factors and symptoms of ovarian cancer. Thus, this study aimed to investigate the level of knowledge of Saudi women about the symptoms and risk factors of ovarian cancer. Methodology: A cross-sectional observational survey was carried out among literate females aged 18 years and above, in Saudi Arabia, using an online self-developed questionnaire that was distributed via a link to Google forms. Only completed surveys were included in the analysis. Results: A total of 473 females responded to this survey. Women who were proactive in talking with their doctors showed a significantly higher score (p value < 0.001). Participants who did not talk to their doctors about ovarian cancer showed a significantly lower score (p value < 0.001). Also, 89.8% of the females mentioned that they did not discuss ovarian cancer with their doctors on any previous visits, where 41.3% of the respondents mentioned that they did not believe that they were in danger, and 5.6% of the females mentioned that their doctors were too busy to talk with them. Conclusion: A poor level of knowledge, poor practices, and behavior toward ovarian cancer among females was observed in Saudi Arabia. Further studies are required to explore the reasons behind this poor knowledge about ovarian cancer.

Single nucleotide polymorphism of transforming growth factor-β1 and interleukin-6 as risk factors for ovarian cancer.

IntroductionWe investigated the association between common variants in TGF-β1, IL-6 and the risk of ovarian cancer (OC) in Tunisian patients and control women.Material, methods and resultsStudy subjects comprised 71 OC cases and 74 control women. Genotyping of TGF-β1 and IL-6 SNPs was done by real-time PCR. No differences were noted in the minor allele frequencies of the three TGF-β1 SNPs between OC patients and controls. However, marked differences in the distribution of TGF-β1 rs1800469 genotypes were seen between OC cases and controls (p < 0.001), with TGF-β1 rs1800469 heterozygous (C/T) genotype being negatively associated with OC (OR [95% CI] = 0.24 [0.15-0.58]). The allelic and genotypic distributions at IL-6 polymorphisms showed a positive association between minor allele (G) at IL-6 rs1880242 variant (p = 0.0275; R [95% CI] = 1.88 [1.03-3.46]) and the occurrence of OC. In fact, the presence of T allele [G/T + T/T] decrease the risk of OC (p = 0.021; OR [95% CI] = 0.38 [0.17-0.88]). In addition, the Haploview analysis demonstrated high linkage disequilibrium (LD) between IL-6 SNPs and eight-locus haplotype analysis identified that GGAGGGGA and GGAGGGTA haplotypes are positively associated with OC risk. A negative association was shown between IL-6 haplotype (TGGGCCTA) and OC occurrence.ConclusionsOur results suggest that TGF-β1 rs1800469, IL-6 rs1880242 variants and IL-6 haplotype (TGGGCCTA) have protective roles of OC risk. IL-6 haplotypes (GGAGGGGA and GGAGGGTA) increase OC susceptibility among Tunisian women.

Reproductive and Hormonal Factors and Risk of Ovarian Cancer by Tumor Dominance: Results from the Ovarian Cancer Cohort Consortium (OC3).

Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells. We pooled data from 9 prospective studies participating in the Ovarian Cancer Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance. Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer (P heterogeneity = 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors (P heterogeneity = 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors (P heterogeneity = 0.08). These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin. Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.

Cancer Prevention in Primary Care: Perception of Importance, Recognition of Risk Factors and Prescribing Behaviors

PurposeAcceptability and uptake of cancer preventive interventions is associated with physician recommendation, which is dependent on physician familiarity with available preventive options. The goal of this study is to evaluate cancer prevention perceptions, understanding of breast and ovarian cancer risk factors, and prescribing behaviors of primary care physicians. MethodsWe conducted cross-sectional. Web-based survey of 750 primary care physicians (250 each for obstetrics/gynecology, internal medicine, and family medicine) in the United States. Survey respondents were recruited from an opt-in health care provider panel. ResultsPerception of importance and the practice of recommending general and cancer-specific preventive screenings and interventions significantly differed by provider type. These perceptions and behaviors reflected the demographics of the population that the primary care physicians see within their respective practices. The majority of respondents recognized genetic/hereditary risk factors for breast or ovarian cancer, while epidemiologic or clinical risk factors were less frequently recognized. Prescribing behaviors were related to familiarity with the interventions, with physicians indicating that they more frequently reinforced a specialist's recommendation rather than prescribed a preventive intervention. ConclusionsCancer prevention perceptions, recognition of cancer risk factors, and prescribing behaviors differ among practice types and were related to familiarity with preventive options. Cancer prevention education and risk assessment resources should be more widely available to primary care physicians.

Identifying sequence variants contributing to hereditary breast and ovarian cancer in\xa0BRCA1 and BRCA2 negative breast and ovarian cancer patients

Families with breast and ovarian cancer are often tested for disease associated sequence variants in BRCA1 and BRCA2. Pathogenic sequence variants (PVs) in these two genes are known to increase breast and ovarian cancer risks in females. However, in most families no PVs are detected in these two genes. Currently, several studies have identified other genes involved in hereditary breast and ovarian cancer (HBOC). To identify genetic risk factors for breast and ovarian cancer in a Norwegian HBOC cohort, 101 breast and/or ovarian cancer patients negative for PVs and variants of unknown clinical significance (VUS) in BRCA1/2 were screened for PVs in 94 genes using next-generation sequencing. Sixteen genes were closely scrutinized. Nine different deleterious germline PVs/likely pathogenic variants (LPVs) were identified in seven genes in 12 patients: three in ATM, and one in CHEK2, ERCC5, FANCM, RAD51C, TP53 and WRN. Additionally, 32 different VUSs were identified and these require further characterization. For carriers of PV/LPV in many of these genes, there are no national clinical management programs in Norway. The diversity of genetic risk factors possibly involved in cancer development show the necessity for more knowledge to improve the clinical follow-up of this genetically diverse patient group.

Germline mutations in Thai patients with nonmucinous epithelial ovarian cancer.

BACKGROUNDGenetic testing is widely recommended for all epithelial ovarian cancer (EOC) patients. However, an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma (HGSC) subtype. HGSC has been reported to be the most common subtype of EOC worldwide (approximately 70%). However, this subtype is less prevalent in Thai patients (reported as only 20%). The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.AIMTo evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.METHODSThis cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital. Clinical risk factors for hereditary ovarian cancer were defined as follows: Age below 40 years, a significant family history of cancer, synchronous ovarian and endometrial cancer, and HGSC. Comprehensive germline mutations were detected by next-generation sequencing.RESULTSOf a total of 112 patients, 82 (73.2%) patients had ≥ 1 risk factor and 30 (26.8%) patients had no risk factors. Germline mutations were detected in 26 patients: 20 (17.8%) patients had BRCA1/2 mutations, but 6 (5.4%) patients had mutations in other genes, including 1 in MLH1, 1 in MSH2, 1 in RAD51C, 2 in ATM and 1 in CDH1. Germline mutations were only detected in patients with risk factors (26 of 82, 31.7%), not in patients without risk factors (P < 0.001). A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations (56.3% vs 10% for those with and without a history of cancer, respectively, 40.8% vs 9.5% for those with and without HGSC). Germline BRCA mutations were detected in 38.8% of patients with HGSC but in only 1.6% of those with non-HGSC. An age below 40 years, personal history of breast cancer, and synchronous ovarian and endometrial cancer were not significant factors (14.3% vs 23.5%, 33.3% vs 21%, 22.2% vs 22.3%).CONCLUSIONApproximately one-third of EOC patients with risk factors had germline mutations. Almost all germline BRCA mutations were found in patients with the HGSC subtype. Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.

Abstract TMIM-074: IGF2 IN HUMAN FOLLICULAR FLUID PROMOTES LYMPHOMAGENESIS IN MAMMARY FAT PAD OF TRP53-NULL MICE, DEPENDING ON ESTROGEN IN MICROENVIRONMENT

Abstract Ovulation overdrive is the most important risk factor of ovarian cancer. In previous study we discovered that preovulatory follicular fluid (FF) collected from IVF women, upon weekly injections into the mammary fat pad of Trp53-null mice for 7 weeks, could induce early onset of B cell lymphomas. In subsequent studies (Abstract by Chu TY et al.), we disclosed the IGF-axis signaling conferred by FFs is responsible for the stemness, clonal expansion and transformation of fallopian tube fimbrial epithelial cells where IGF2 in FF bound IGF-1R on secretory cells to activate the downstream PI3K/Akt/mTOR and PI3K/Akt/NANOG signaling pathways for the transformation. In this study, we identified the same IGF2 is also responsible for the FF-induced lymphomagenesis in Trp53-null mice. When IGF2 was depleted from FF, the tumorigenesis rate reduced from 10/18 (56%) to 1/6 (17%). On the other hand, injections with pure IGF2 (100 mg/ml) grew tumors in 33% (2/6) of mice. The same injection to Trp53 wild type did not grow tumor. We also found a microenvironment of adipose tissue seemed to be important for the FF-induced lymphomagenesis. The same injections of FF into the subcutis and other sites did not grow tumor. Additionally, tumor development depends not only on the injection site but also on the female sex hormone and ER function. No tumor growth was observed in castrated female mice and in male mice. Adding fulvastrant to the injections resulted in complete shrinkage of tumor. Meanwhile, extended injection of FF from 7 weeks to 13 weeks promoted tumor progression but did not increase tumor incidence. The findings suggest a transformation activity of human preovulatory FF largely conferred by IGF2. In the context of germline Trp53 loss, this activity likely promotes expansion of the lymphocytic progenitors that have already been transformed. Meanwhile, we found ER is expressed in the tumor adjacent adipocytes but not in the lymphoma cells. Also, ER antagonist, although largely confined tumor growth, did not decrease the tumor incidence. In this tumorigenesis model conferred by Trp53 loss and FF-IGF2, estrogen seems to play an essential role in tumor progression but not in tumor initiation, and this promotion effect is through the adipocyte microenvironment. Citation Format: Hsuan-Shun Huang, Sung-Chao Chu, Tang-Yuan Chu. IGF2 IN HUMAN FOLLICULAR FLUID PROMOTES LYMPHOMAGENESIS IN MAMMARY FAT PAD OF TRP53-NULL MICE, DEPENDING ON ESTROGEN IN MICROENVIRONMENT [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-074.

Douching, Talc Use, and Risk for Ovarian Cancer and Conditions Related to Genital Tract Inflammation.

Douching is associated with disorders involving genital tract inflammation and genital talc use with epithelial ovarian cancer (EOC), but their joint effects are infrequently considered. From 2,040 cases of EOC and 2,100 controls enrolled in eastern Massachusetts and New Hampshire, we used unconditional logistic regression to estimate risk for EOC associated with douching and/or talc use. In subsets of cases and controls, we also collected information about pelvic inflammatory disease (PID), ectopic pregnancy, and cervical neoplasia to estimate risk for these events from douching and/or talc use. The adjusted OR and 95% confidence interval (CI) for all EOC was 0.94 (0.76-1.16) in women who douched but never used talc and 1.28 (1.09-1.51) in women who used talc but never douched. Compared with women who never regularly douched or used talc, ORs (95% CIs) were 0.83 (0.52-1.33) for women who both used talc and homemade douches and 1.53 (1.11-2.10) for women who both used talc and store-bought douches. Cases who both douched and used talc were more likely to have had PID compared with cases who had used neither [OR = 5.03 (95% CI, 1.61-15.7)]. Douching is not an independent risk factor for ovarian cancer, but the combination of talc use and store-bought douches may modestly increase the risk for EOC beyond that for talc use alone. The joint effect of talc use and douching, especially with commercial products, should be considered in evaluating risks associated with disorders involving genital tract inflammation or EOC.

Identifying modifiable and non-modifiable risk factors of epithelial ovarian cancer—can we get it better?

Ovarian cancer is the fifth most common cancer in women worldwide, with an estimated lifetime risk of one in 54–75, and one in 100 of ovarian cancer-related mortality (1). The role of irreversible and reversible risk factors in development of epithelial ovarian cancer (EOC) has been researched extensively, with a heavy focus on genetic factors and family history of breast/ovarian cancer.

Urinary PGE-M Levels and Risk of Ovarian Cancer.

Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

Principles of diagnosis of ovarian neoplasms — minimization of errors

Ovarian cancer mortality rates hold a leading position among women’s cancer, which is primarily associated with the pathogenetic features of ovarian cancer, the heterogeneity of the disease, the lack of effective screening and diagnostic methods for early cancer detection. The causes of most ovarian tumors remain unknown. Ovarian benign tumors and tumor-like formations are not among the risk factors of ovarian cancer. The purpose of this literature review is to highlight the latest data from world expert organizations on the possibilities of ovarian neoplasm diagnosis and treatment.

Posttraumatic Stress Disorder Is Associated with Increased Risk of Ovarian Cancer: A Prospective and Retrospective Longitudinal Cohort Study.

Ovarian cancer is the deadliest gynecologic cancer. Chronic stress accelerates tumor growth in animal models of ovarian cancer. We therefore postulated that posttraumatic stress disorder (PTSD) may be associated with increased risk of ovarian cancer. We used data from the Nurses' Health Study II, a longitudinal cohort study with 26 years of follow-up, conducted from 1989 to 2015 with 54,710 subjects. Lifetime PTSD symptoms were measured in 2008. Self-reported ovarian cancer was validated with medical records. Risk of ovarian cancer was estimated with Cox proportional hazards models and further adjusted for known ovarian cancer risk factors (e.g., hormonal factors) and health risk factors (e.g., smoking). Fully prospective secondary analyses examined incident ovarian cancer occurring after PTSD assessment in 2008. In addition, we examined associations by menopausal status. During follow-up, 110 ovarian cancers were identified. Women with high PTSD symptoms had 2-fold greater risk of ovarian cancer versus women with no trauma exposure [age-adjusted HR = 2.10; 95% confidence interval (CI), 1.12-3.95]. Adjustment for health and ovarian cancer risk factors moderately attenuated this association (HR = 1.86; 95% CI, 0.98-3.51). Associations were similar or moderately stronger in fully prospective analyses (age-adjusted HR = 2.38; 95% CI, 0.98-5.76, N cases = 50) and in premenopausal women (HR = 3.42; 95% CI, 1.08-10.85). In conclusion, we show that PTSD symptoms are associated with increased risk of ovarian cancer. Better understanding of the underlying molecular mechanisms could lead to interventions that reduce ovarian cancer risk in women with PTSD and other stress-related mental disorders. SIGNIFICANCE: PTSD is associated with ovarian cancer risk, particularly in premenopausal women. Understanding the underlying molecular mechanisms will aid in formulating ways to reduce ovarian cancer risk associated with chronic stress.

Identification of a FAS/FASL haplotype associated with endometriosis in Iranian patients

Risk factors for ovarian cancer include a number of genetic variants as well as endometriosis. The FAS–FASL system is one of the apoptotic pathways that play an essential role in the apoptotic process within the endometrium. Here, we evaluate the correlation between FAS–FASL polymorphisms with the risk of endometriosis in Iranian patients and healthy controls. We extracted DNA from whole blood samples using a DNA Purification Kit. Using the PCR-RFLP method, three SNPs, including FAS (-670 A/G) and FASL (-844 C/T and _124G/A) genes, were genotyped in 112 patients with endometriosis as well as 110 healthy controls. The frequency of genotypes and the alleles of these SNPs were analyzed by the chi-squared test for the significant association. Haplotype analysis was done by the PLINK software. The frequency distribution of haplotypes was significant between SNPs so that the ACG haplotype was more frequent in the cases than in the controls (p = .017). These results indicate that haplotype analysis can be useful for SNP analysis. The ACG haplotypes in FAS-670A/G, FASL-844C/T, and _124G/A genes may be correlated with the progression of endometriosis.

Endometriosis-associated ovarian cancer occurs early during follow-up of endometrial cysts.

Endometriosis is a risk factor for ovarian cancer. Endometriosis-associated ovarian cancer (EAOC), most commonly clear cell carcinoma, is believed to develop from ovarian endometrial cysts. In this study, we reviewed published cases of EAOC considered to have developed from endometrial cysts, and focused on the observation period. We searched for articles published since January 2000 that reported cases of ovarian cancer thought to have originated from endometrial cysts using PubMed, Web of Science, and Ichushi-Web. The period from the start of follow-up of the endometrial cyst to the diagnosis of ovarian cancer was calculated. Seventy-nine cases were identified from 32 articles. The median period from the diagnosis of endometrial cysts to the diagnosis of ovarian cancer was only 36months. Approximately 75% of cases developed into cancer within 60months and most cases developed within 120months. Our results suggest that clinically detectable cysts subsequently diagnosed as ovarian cancer might already have contained cancer cells. Therefore, the mechanism of EAOC development needs to be re-examined and appropriate management guidelines need to be developed.