Risk Factors For Endometrial Cancer Research Articles

Abstract PR003: The combination of the glucagon like peptide-1 receptor agonist semaglutide and the progestin levonorgestrel is highly effective in preclinical studies of endometrial cancer

Abstract Obesity is a major risk factor for endometrial cancer (EC), and glucagon like peptide-1 receptor (GLP-1R) agonists such as semaglutide may be helpful to achieve weight loss during conservative treatment or for EC prevention. Progestins such as levonorgestrel are effective in preventing or treating early-stage EC. However, better and more durable response rates could be achieved using combinatorial therapeutic regimens of well tolerated agents with the potential to enhance progestin effectiveness. We theorized that the combination of semaglutide and levonorgestrel would be useful as a novel treatment or prevention regimen and tested this hypothesis using EC cell lines, patient-derived organoids, and RNA-sequencing from patient samples. From the molecular perspective, EC cell lines, organoids, and tissues express GLP-1R as determined by both qPCR and Western blotting, and GLP-1R agonist treatment induces GLP-1R mRNA transcription through positive feedback mechanisms in EC cell models. Preclinical studies in 6 patient-derived organoid models of EC demonstrated the promising therapeutic effects of the combination of semaglutide and levonorgestrel on endometrial cell viability. Specifically, patient-derived organoids from grade 1 endometrial carcinomas were treated with progesterone, levonorgestrel, semaglutide, or levonorgestrel + semaglutide at drug concentrations of 100 nM for 72 hours. Multiple models demonstrated a significant reduction in viability in response to combinatorial treatment. Most interesting was the induction of not only the membrane GLP-1 receptor with treatment, but also the significant upregulation of nuclear and membrane progesterone receptors, PR and PGRMC1/2, respectively, indicating a positive feedback loop between semaglutide and progestins such as levonorgestrel. In addition, other steroid hormone receptor mRNAs such as the estrogen, androgen and mineralocorticoid receptors (ER, AR, and MR) were similarly upregulated. In these studies, we identify synergistic molecular crosstalk between the GLP-1R and steroid hormone receptor pathways with the potential to enhance the anti-cancer activity of semaglutide and levonorgestrel when combined. Future studies are aimed at testing this regimen in patients conservatively managed for atypical endometrial hyperplasia or low-grade endometrial cancers. Citation Format: Kimberly K. Leslie, Andrea Hagemann, Kristina Thiel, Ian Hagemann, David Mutch, Eric Devor, Paige Malmrose. The combination of the glucagon like peptide-1 receptor agonist semaglutide and the progestin levonorgestrel is highly effective in preclinical studies of endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR003.

Abstract IA005: New directions in prevention and early detection of endometrial cancers

Abstract Most endometrial cancers and precursor lesions are preceded by postmenopausal bleeding (PMB), offering a window of opportunity for early detection and improved survival. Clinical guidelines recommend prompt evaluation of PMB to rule out endometrial cancer. Current diagnostic approaches including transvaginal ultrasound and endometrial biopsy are invasive and can be associated with discomfort and procedural pain, and we have shown that recommendations may not be consistent with underlying risk of endometrial cancer. Access to these procedures may be challenging for patients who live in rural areas or who experience other barriers to care. Current strategies may also have limited accuracy for detecting non-endometrioid cancers which are clinically aggressive, more common in Black women, and increasing in incidence and mortality in the U.S. Black women experience significant racial disparities in endometrial cancer survival and are more likely to experience diagnostic delays compared to their White counterparts. Because of the anatomical continuity of the lower genital tract, we and others have demonstrated the feasibility of pairing molecular assays with minimally invasive self-sampling approaches, such as vaginal tampons, for the detection of tumor DNA. In a recent study led by our colleagues at the Mayo Clinic, we identified over 28 methylation markers that were tested in self-collected tampon samples that showed good clinical performance for endometrial cancer detection. Such approaches can mitigate cancer disparities by offering an at-home early detection strategy to increase coverage and expand access to care. To date, few endometrial cancer studies have been conducted within diverse clinical populations. To address this gap, we designed the Discovery and Evaluation of Tests for Endometrial Cancer in Tampons (DETECT) study. DETECT is a case control study that includes patients undergoing hysterectomy for endometrial cancer and benign conditions at the University of Alabama at Birmingham (UAB). DETECT has enrolled over 700 patients to date, including over 360 with endometrial cancer (approximately 30% with non-endometrioid tumors). In this study, we collect extensive questionnaire data including information about symptoms, and novel risk factors such as feminine hygiene and hair product use. We obtain clinical information on diagnostic procedures, surgery, and treatment information from electronic medical records, and collect tampon, tissue, and blood samples from enrolled patients. In preliminary analyses, over two-thirds of participants self-collected a vaginal tampon sample, with collection varying by race (57% in Black vs. 76% in White patients). Next steps include pilot testing to compare the performance of biomarkers (somatic mutations and methylation markers) measured from tampon samples to tissue for endometrial cancer detection. Future goals of DETECT include the evaluation of endometrial cancer risk factors, biomarkers, outcomes, and disparities across the cancer continuum. Citation Format: Megan A. Clarke. New directions in prevention and early detection of endometrial cancers [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA005.

Abstract PR001: Highlighting the combined effects of BMI and polygenic risk score on endometrial cancer risk

Abstract Obesity is more strongly associated with endometrial cancer risk than any other cancer type. However, the extent to which genetic susceptibility influences the risk of endometrial cancer independent of obesity remains unknown. Thus, this study aimed to evaluate the predictive performance of polygenic risk score (PRS), body mass index (BMI) and other factors in determining endometrial cancer risk, as well as to explore joint effects on endometrial cancer. PRS was generated using 1.1 million HapMap3 variants from the largest published endometrial cancer genome-wide association study. An endometrial cancer prediction model was constructed using established endometrial cancer risk factors (age, BMI, number of live births, ever taken oral contraceptive pill, age of menarche, and predicted age of menopause). Additionally, an integrated prediction model was constructed, combining the endometrial cancer PRS with established risk factors. The ability of models to predict endometrial cancer status was assessed in unrelated participants of European ancestry from the UK Biobank cohort, encompassing 1,867 participants with endometrial cancer (860 incident cases) and 133,322 cancer-free controls. The integrated model including PRS and risk factors had a modest yet statistically significant improvement in prediction of endometrial cancer status, compared with the model using risk factors alone (AUC 0.752 versus 0.741; P = 1.28 × 10−7). When examining incident cases, participants in the middle and top tertiles of the PRS distribution had a 1.96- (95% CI 1.39-2.77; P = 1.28 × 10−4) and 3.03-fold (95% CI 2.01-4.58; P = 1.60 × 10−8) elevated risk of developing endometrial cancer, respectively, in contrast to those in the lowest tertile. As expected, elevated BMI was associated with increased endometrial cancer risk. Compared to participants with a normal BMI, overweight participants (25kg/m2 ≤ BMI < 30kg/m2) had a 1.58-fold increased hazard ratio (HR; 95% CI 1.32-1.90; P = 8.43 × 10−7), while obese participants (BMI ≥ 30kg/m2) a 3.23-fold increased HR (95% CI 2.71-3.85; P < 2.00 × 10−16). Notably, we observed multiplying effects of BMI and PRS on endometrial cancer risk, with obese participants in the top tertile of the PRS distribution having a 7.53-fold increased HR (95% CI 3.78-14.99; P = 9.41 × 10−9). In summary, these findings indicate that higher PRS was associated with endometrial cancer risk, irrespective of BMI. Moreover, the integration of PRS with established risk factors may aid in better stratifying the general population for their susceptibility to endometrial cancer. Citation Format: Tracy A. O'Mara, Xuemin Wang, Laure Dossus, Marc J. Gunter, Emma J. Crosbie, Dylan M. Glubb. Highlighting the combined effects of BMI and polygenic risk score on endometrial cancer risk [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr PR001.

Obesity and metabolic syndrome as risk factors for endometrial cancer

Obesity and metabolic syndrome as risk factors for endometrial cancer

The Womb Cancer Awareness Measure (WCAM): development of an instrument to assess public awareness of endometrial cancer

ObjectiveTo develop and test a novel instrument to assess public awareness of endometrial cancer symptoms and risk factors in a UK population.MethodsA 36-item questionnaire was developed through literature review and...

Impact of weight loss after treatment on survival outcomes of overweight and obese patients with early‑stage endometrial cancer.

Despite the fact that obesity is the main risk factor for endometrial cancer, there is limited evidence regarding the effects of body weight change on overweight and obese women treated for early-stage endometrial can its impact on cancer outcomes. A retrospective cohort study was performed including all overweight and obese patients with early-stage type-I endometrial cancer that were treated at the Insular University Hospital of Las Palmas (Las Palmas de Gran Canaria, Spain) between January 2007 and December 2019. Body weight change at 12 months of treatment was evaluated, as well as its impact on cancer outcomes. Weight loss ≥5% was independently evaluated regarding its impact on survival. A total of 526 women were studied, of which 152 (28.90%) were overweight (BMI ≥25 and <30) and 374 (71.10%) were obese (BMI ≥30). The median follow-up was 76.17 months, during which time 77 (14.64%) women died. In the survivor group, body weight at initial diagnosis was 86.4±17.9 kg compared with 84.6±16.4 kg 1 year after treatment, which corresponded to a significant mean weight loss of 1.47 kg (P<0.001). However, in the group of non-survivors, body weight at initial diagnosis was 84.7±15.7 kg compared with 84.7±14.6 kg 1 year after treatment, which demonstrated a non-significant mean weight loss of 0.63 kg (P=0.180). When comparing between the patients who maintained or gained ≥5% weight and those who lost ≥5% weight, there were no significant differences taking into account the whole cohort and follow-up time; however, when adjusting for the period between 32 and 98 months, survival was significantly higher in those patients that lost ≥5% of their initial body weight (P=0.025; log-rank test). Based on the final univariate and cer and multivariate analyses, body weight change at 12 months was not indicated to be a factor significantly affecting overall survival; adjusted hazard ratio was 1.01 (95% CI 0.97-1.05, P=0.723). In conclusion, even if greater weight loss is observed in patients with endometrial cancer that survive the disease, no significant impact on survival outcomes is observed based on multivariate analysis.

Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer

PurposeThe study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC).Materials and methodsA total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters—standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)—to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction.ResultsOur study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression.ConclusionThe present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.Graphic

Abstract B100: Using a plant-based diet and exercise to improve outcomes in African American postmenopausal breast and endometrial cancer survivors

Abstract Background: Obese postmenopausal African American (AA) women with breast and endometrial cancer are at increased risk of recurrence. Obesity and aging have been associated with changes in the gut microbiota. Plant-based diets, such as soy isoflavone consumption may protect against breast and endometrial cancer. Methods: A mixed-methods, lifestyle intervention study was conducted to evaluate adoption of a whole-food plant-based diet, physical activity, and changes in risk for breast and endometrial cancer among obese, post-menopausal AA women. We examined acceptability and feasibility of adopting a whole-food, plant-based diet and the effect of the diet on reductions in weight, adiposity, inflammation, circulating estrogen, and gut microbiome profile. Results: In 5 focus group discussions, 20 AA women described their knowledge of breast and endometrial cancer risk factors, attitude toward a plant-based diet, experience with making lifestyle changes, and preferences for plant-based alternatives to traditional meat-based meals. This feedback was used to tailor the 4-weeks of plant-based produce boxes provided to the women. Women report being pleased with the food selections; document adherence to the meals and physical activity with food and exercise tracking. Gut microbiome analysis is underway. Conclusion: This study addresses knowledge gaps in breast and endometrial cancer risk and behavioral modifications affecting risk among an obese, post-menopausal AA female population. The long-term goal of this program of research will shed light on the mechanisms involved in the gut microbiome and the contributions of changes to these systems on declining health. Citation Format: Desiree A. Rivers, Regina Leonis, Zakirah A. Abdul-Hameed, Shaliesh A. Singh, Brian A. Rivers. Using a plant-based diet and exercise to improve outcomes in African American postmenopausal breast and endometrial cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B100.

Causal effects of exposure to ambient air pollution on cancer risk: Insights from genetic evidence

Air pollution has been increasingly linked to cancer risk. However, the genetic causality between air pollution and cancer risk remains poorly understood. To elucidate the potential roles of air pollution (NOx, NO2, PM2.5, PM course, and PM10) in the risk of 18 specific-site cancers, large-scale genome-wide association studies with a novel Mendelian randomization (MR) method were employed. Our MR analyses revealed significant associations between certain air pollutants and specific types of cancer. Specifically, a positive association was observed between NOx exposure and squamous cell lung cancer (OR: 1.96, 95%CI: 1.07–3.59, p = 0.03) as well as esophageal cancer (OR: 1.002, 95%CI: 1.001–1.003, p = 0.005). Genetically predicted NO2 exposure was found to be a risk factor for endometrial cancer (OR 1.41, 95%CI: 1.03–1.94, p = 0.03) and ovarian cancer (OR: 1.49, 95%CI: 1.14–1.95, p = 0.0037). Additionally, genetically predicted PM2.5 exposure was associated with an increased risk of ER+ breast cancer (OR: 1.24, 95%CI: 1.03–1.5, p = 0.02) and ER- breast cancer (OR: 2.57, 95%CI: 1.05–6.3, p = 0.04). PM course exposure was identified as a risk factor for glioma (OR: 487.28, 95%CI: 13.08–18,153, p = 0.0008), while PM10 exposure exerted a detrimental effect on mesothelioma (OR: 114.75, 95%CI: 1.14–11,500.11, p = 0.04) and esophageal cancer (OR: 1.01, 95%CI: 1.007–1.02, p = 0.03). These findings underscored the importance of mitigating air pollution to reduce the burden of cancer and highlight the need for further investigations to elucidate the underlying mechanisms involved in these associations.

Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.

Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies. We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates. The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031). Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

Incessant ovulation: a review of its importance in predicting cancer risk.

Estrous cycles are recurring changes in therian mammals induced by estrogen, progesterone, and other hormones culminating in endometrial proliferation, ovulation, and implantation if fertilization occurred. In women, the estrous cycle is the menstrual cycle; but, unlike most mammals, the end of an infertile cycle is marked by endometrial sloughing and the start of another without an anestrous phase. Women stop cycling at menopause, while in most mammals, cycles continue until death. Epidemiologic studies identified menarche, menopause, births, lactation, and oral contraceptive (OC) use as key risk factors for ovarian, breast, and endometrial cancers. A composite variable was created to estimate the number of cycles not interrupted by events that stop ovulation. Captured by the phrase "incessant ovulation", repetitive cycles were first postulated to affect ovarian cancer risk and later extended to breast and endometrial cancers. These associations could be explained by cumulative effects of repetitive tissue changes within reproductive organs, immune consequences of repetitive ovulation through the glycoprotein mucin 1, and residual effects of past ovulations that enhance ovarian production of testosterone. The latter two pathways could affect the risk for cancers in other organs not considered "reproductive".

SAT370 Economic Burden of Endometrial Cancer Associated with Polycystic Ovary Syndrome

Abstract Disclosure: L.A. Pace: None. D. Markovic: None. R.P. Buyalos: Employee; Self; Fertility and Surgical Associates of California. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Spruce Biosciences, Fortress Biotech, Core Access Surgical Technologies. Grant Recipient; Self; Foundation for Research and Education Excellence, Ferring Pharmaceuticals. Stock Owner; Self; Martin Imaging. Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive aged females, affecting approximately 6 million U.S. women. Endometrial cancer, in turn, is the most common gynecological malignancy and the fourth most common cancer overall in female patients. Objectives: To assess the excess economic burden associated with endometrial cancer in women with PCOS. Method: Using PRISMA guidelines for systematic review, we searched PubMed, Web of Science, Scopuse, and Embase for all studies on endometrial cancer in patients with known PCOS. Excluded studies were reviews and case reports, those not conducted in human subjects, without controls, without full text available, or reporting solely on diseases other than PCOS. Selected studies were assessed for quality using the Newcastle-Ottawa Scale. Meta-analysis was performed using the DerSimonian-Laird random effects model to assess the pooled risk ratio (RR) for the association between PCOS and endometrial cancer, then calculation of the excess cost was assessed in U.S. dollars (USD), adjusted for inflation using a medical care inflation calculator. Result: We screened 98 studies by title and abstract, 32 titles in full text, and included 11 articles. Pooled RR was 2.90 (95% CI 1.57-5.37), p=0.0196. In the U.S., overall prevalence of endometrial cancer in patients with PCOS is 0.409%, compared with baseline estimated five-year prevalence (2014-2019) of endometrial cancer in all women of 0.141%, or 235,596 cases. The excess prevalence of endometrial cancer in women with PCOS is therefore 0.2679%, or approximately 361 women. Direct healthcare costs associated with endometrial cancer per patient per year were estimated to be $8,597, when adjusted for inflation to 2022 costs. Therefore, the excess cost of endometrial cancer related to PCOS is estimated at 361 x $8,597 = $3.1 million per year in 2022 USD. Conclusion: In 2022 USD, the excess annual healthcare cost for endometrial cancer care in patients with PCOS exceeds $3 million per year. While the overlap between the risk factors and pathophysiologic underpinnings of both conditions is well-known, PCOS is not always directly addressed as a risk factor for endometrial cancer. Given the findings of this meta-analysis, taken in combination with previously collected data estimating the annual healthcare costs associated with PCOS diagnosis and treatment alone, to exceed $2 billion, we advocate for and increased focus in the global health, policy, and scientific communities to better address this condition and its sequelae. Funding: Foundation for Research and Education Excellence Presentation Date: Saturday, June 17, 2023

Oncoguía de cáncer de endometrio 2023

In Mexico, endometrial cancer ranks fifth in incidence and is the second cause of gynecological cancer after cervical cancer. The main risk factor for endometrial cancer is obesity and other conditions related to metabolic syndrome. The symptom that indicates the start of the approach is abnormal uterine bleeding, especially in postmenopausal patients. The standard of initial treatment for apparently localized endometrial cancer is hysterectomy. Lymph node evaluation provides relevant information on the prognosis and the need for adjuvant therapy. Various clinical and histological parameters have been associated with the survival of these patients. Additionally, data from the Cancer Genome Atlas project has increased our understanding of endometrial cancer's biological and prognostic heterogeneity. Several studies have evaluated the role of different adjuvant strategies, such as brachytherapy, radiotherapy, and chemotherapy. In advanced diseases, standard treatment consists of systemic therapy and other options include chemotherapy, hormone therapy, and immunotherapy. Surgery and radiation therapy can sometimes improve outcomes for patients with advanced disease. These guidelines aim to share with the oncology community the diagnostic and treatment strategies used at the National Cancer Institute to diagnose and treat endometrial cancer.

Assessment of Serum Zn, Cu, Mn, and Fe Concentration in Women with Endometrial Cancer and Different Endometrial Pathologies.

There is conflicting evidence on the effect of specific micronutrient concentration and cancer risk. In this study, we investigated the differences in serum zinc, copper, iron, and manganese levels and different endometrial pathologies, including endometrial cancer. 110 patients with a confirmed diagnosis of endometrial cancer, benign uterine conditions (endometrial polyp, endometrial hyperplasia, uterine myoma), or normal endometrium were included in the study and assessed in terms of endometrial cancer risk factors. The measurements of serum micronutrients were conducted using inductively coupled plasma optical emission spectrometry. When assessing for differences between serum concentrations of trace metals, we found significant differences in the distribution of Mn (p < 0.001) and Fe (0.034). There was also a significant difference in Cu/Zn ratio between the analyzed groups (p = 0.002). Patients' BMI was found to influence Cu concentration, with obese patients having higher mean copper concentration (p = 0.006). Also, patients' menopausal status was shown to influence Cu concentration with postmenopausal patients having higher Cu levels (p = 0.001). The menopausal status was found to influence Cu/Zn ratio (p = 0.002). Univariable regression analysis did not confirm that any of the micronutrients significantly influence the risk of endometrial cancer. The concentration of specific trace metals varies between different histopathological diagnoses of endometrial pathologies. Menopausal status and patient BMI are endometrial cancer risk factors impacted by the concentrations of Cu and Zn and their ratio.

Metabolic syndrome score as an indicator in a predictive nomogram for lymph node metastasis in endometrial cancer

BackgroundLymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer.MethodsThis study is based on patients diagnosed with EC in Peking University People’s Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors.ResultsThe prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size > = 2 cm, myometrial invasion > = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81–0.90) and 0.77 (95% CI: 0.77–0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82–0.93) and 0.80 (95% CI: 0.74–0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value.ConclusionThis model may promote risk stratification and individualized treatment, thus improving the prognosis.

Association between Provider-Patient Relationship, Communication, Accessibility Convenience, and Perceived Quality of Care from Patients Living with HIV before and during SARS-Cov-2 Pandemic

OBJECTIVE The study aims to determine the risk factors for endometrial hyperplasia and endometrial cancer in patient with abnormal uterine bleeding and thus early diagnostic investigations to detect the disease and limit its development. DESIGN Primary data were collected from an infectious disease clinic outpatient setting using the PSQ-18 short form. The data were collected between February and March 2021. The study population included (a) non-institutionalized individuals, (b) individuals aged 18 years and older, (c) individuals living with HIV/AIDS, and (d) individuals who had had a provider visit in the past 12 months at an infectious disease clinic. METHODS Multiple regression was used to assess the relationship between the dependent and independent variables using a cross-sectional quantitative analysis. RESULTS The study revealed a statistically significant relationship between PPR and perceived quality of care from the perspective of patients living with HIV before and during the SARS-CoV-2 pandemic. CONCLUSION The study results indicated that overall provider-patient relationship (PPR), communication, accessibility, and convenience were related to perceived quality of care. The study findings also revealed that PPRs can uniquely impact perceived quality of care. Provider accessibility was also found to uniquely impact a patient’s perceived quality of care. Finally, the study results demonstrated that HIV patients who have a good relationship with healthcare providers and a high level of satisfaction tend to perceive high-quality healthcare.

Association of body mass index with early age at diagnosis of endometrial intraepithelial neoplasia

ObjectiveElevated body mass index (BMI) is a risk factor for endometrioid endometrial cancer and its precursor, endometrial intraepithelial neoplasia (EIN). Our objective was to describe the association between BMI and age at EIN diagnosis. MethodsWe conducted a retrospective study of patients diagnosed with EIN from 2010 to 2020 at a large academic medical center. Patient characteristics were stratified by menopausal status and compared using a chi-square or t-test. We used linear regression to determine the parameter estimate (β) and 95% confidence interval for the association between BMI and age at diagnosis. ResultsWe identified 513 patients with EIN; 503 (98%) had complete medical records. Premenopausal patients were more likely to be nulliparous and to have polycystic ovary syndrome than postmenopausal patients (both p ≤ 0.001). Postmenopausal patients were more likely to have hypertension, type 2 diabetes, and hyperlipidemia (all p ≤ 0.02). There was a significant linear association between BMI and age at diagnosis in premenopausal patients (β = −0.19 (95% CI: −0.27, −0.10). In premenopausal patients, for every 1-unit increase in BMI, age at diagnosis decreased by 0.19 years. No association was observed in postmenopausal patients. ConclusionsIn a large cohort of patients with EIN, increasing BMI was associated with an earlier age at diagnosis in premenopausal patients. This data suggests consideration of endometrial sampling in younger patients with known risk factors for excess estrogen exposure.

Modifiable risk factors and risk of colorectal and endometrial cancer in Lynch syndrome: A systematic review and meta-analysis.

e22544 Background: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer. Non-genetic risk factors, including obesity, physical activity, alcohol intake, and smoking are well-established in sporadic cancers but are less studied in Lynch syndrome. A better understanding of these risk factors could directly contribute to cancer prevention. Methods: Searches were conducted on MEDLINE, Embase and Web of Science for retrospective or prospective cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Screening, data extraction and quality assessment were completed by 2 reviewers independently. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for colorectal and endometrial cancer were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462) and the meta-analysis conducted in accordance with PRISMA and MOOSE reporting guidelines. Results: A total of 770 citations were reviewed. Twelve cohort studies involving 12685 patients with Lynch syndrome investigated risk of colorectal cancer, while 3 studies including 1865 patients assessed risk factors for endometrial cancer. Eight colorectal cancer studies were eligible for meta-analysis. Obesity (HR 2.38, 95% CI 1.52-3.73) and alcohol intake (HR 1.43, 95% CI 1.05-1.94) increased colorectal cancer risk, physical activity was protective (HR 0.66, 95% CI 0.52-0.83), and smoking had no effect (HR 1.02 95% CI 0.83-1.27). Type 2 diabetes mellitus and low dietary intake of calcium and multivitamins might increase risk of colorectal cancer, although more studies are needed. There is a paucity of data pertaining to endometrial cancer. In a qualitative synthesis of 3 endometrial cancer cohort studies, female hormonal risk factors and type 2 diabetes mellitus may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Conclusions: Lifestyle recommendations related to weight, physical activity, and alcohol may also be relevant to cancer prevention for individuals with Lynch syndrome and may provide a meaningful adjunct to standard interventions for risk modification. There are very poor data examining modifiable risk factors in endometrial cancer. Further high-quality prospective cohort studies, in particular including endometrial cancer as an endpoint, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

Changes in the expression of cancer- and metastasis-related genes and proteins after metformin treatment under different metabolic conditions in endometrial cancer cells

Research questionHyperinsulinemia and elevated estrogen levels are known risk factors for endometrial cancer (EC) development and are associated with obesity, type 2 diabetes mellitus (T2DM), insulin resistance, among others. Metformin, an insulin-sensitizing drug, displays anti-tumor effects in cancer patients, including EC, but the mechanism of action is still not completely understood. In the present study, the effects of metformin on gene and protein expression were investigated in pre- and postmenopausal EC in vitro models in order to identify candidates that are potentially involved in the drug's anti-cancer mechanism. DesignAfter treating the cells with metformin (0.1 and 1.0 mmol/L), changes in the expression of >160 cancer- and metastasis-related gene transcripts were evaluated with RNA arrays. A total of 19 genes and 7 proteins were selected for a follow-up expression analysis, including further treatment conditions, in order to evaluate the influence of hyperinsulinemia and hyperglycemia on metformin-induced effects. ResultsChanges in the expression of BCL2L11, CDH1, CDKN1A, COL1A1, PTEN, MMP9 and TIMP2 were analyzed on gene and protein level. The consequences resulting from the detected expression changes as well as the influence of varying environmental influences are discussed in detail. With the presented data, we contribute to a better understanding of the direct anti-cancer activity of metformin as well as its underlying mechanism of action in EC cells. ConclusionsAlthough further research will be necessary to confirm the data, the influence of different environmental settings on metformin-induced effects could be highlighted with the presented data. Additionally, gene and protein regulation were not similar in the pre- and postmenopausal in vitro models.

Endometrial cancer: Pathophysiology, diagnosis and management

The most prevalent gynecologic disease is cancer of the endometrium, In the US, it is the fourth most prevalent malignancy in women after breast, lung, and colorectal malignancies. Despite a steady prevalence of sickness, during the past 20 years, the death rate has climbed by more than 100%. The risk factors of endometrial cancer includes unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or inability to ovulate, and polycystic ovarian syndrome. Ageing, obesity, hypertension, diabetes mellitus, and genetic nonpolyposis colorectal cancer are additional risk factors. This article presents an overview of endometrial carcinoma's epidemiology, prevention, diagnosis, therapy, and prognosis. Chemotherapy, radiation, surgery, and radiation therapy are all forms of treatment. Nonsurgical treatments can be used to treat endometrial hyperplasia with a low to moderate risk. The likelihood of survival is often determined by the disease stage and histology, with the majority of patients at stages I and II having a good prognosis. Endometrial cancer may be prevented in part by managing risk factors such obesity, diabetes, and hypertension.