Risk Factors For Endometrial Cancer Research Articles

Hypoxia-induced Factor-1α and its Role in Endometrial Cancer.

The transcription factor hypoxia inducible factor-1 (HIF-1) is one of the main factors in the cell's response to a lack of oxygen. Hypoxia is a typical feature of a growing cancerous tumor. Increased activity of HIF-1 is observed in many cancers, including endometrial cancer. HIF-1 functions as a heterodimer consisting of three subunits HIF-1α, HIF-2α, and HIF-3α and one subunit β. HIF-1α is a subunit that is sensitive to oxygen concentration and is constitutively expressed. The HIF-1α gene is highly polymorphic. Literature data suggest that single nucleotide polymorphisms (SNPs) of the HIF-1α gene may be risk factors for endometrial cancer. A better understanding of the molecular mechanisms of cancer development, progression and prognosis, including the role of SNPs, could lead to the development of new anti-cancer therapies.

DNA methylation detection is a significant biomarker for screening endometrial cancer in premenopausal women with abnormal uterine bleeding

ObjectiveThe aim of our study was to explore the value of DNA (CDO1m/CELF4m) methylation detection in exfoliated cervical cells collected for screening endometrial cancer in premenopausal women with abnormal uterine...

Risk Factors for Endometrial Cancer in the World: A Narrative Review of the Recent Literature

Risk Factors for Endometrial Cancer in the World: A Narrative Review of the Recent Literature

Analyzing 10-year time trends for Hysterectomy and Oophorectomy: Focus on Endometrial sampling and risk factors for Endometrial Cancer

Analyzing 10-year time trends for Hysterectomy and Oophorectomy: Focus on Endometrial sampling and risk factors for Endometrial Cancer

The relationship between imaging-based body composition parameters and disease prognosis in patients with endometrial cancer.

Obesity is known as a risk factor for endometrial cancer (EC). Only a few studies investigate the relationship between sarcopenia and sarcopenic obesity and EC. In this study, our aim was to investigate the relationship between the cross-sectional imaging-based body composition parameters and the disease prognosis in low-grade (LG) and high-grade (HG) EC. We conducted a retrospective study in women diagnosed with low and high-grade EC between January 2014 and May 2022 who had abdominal MRI and thorax CT as a part of routine staging workup. We used the skeletal muscle index (SMI) at the level of the third lumbar vertebra to assess sarcopenia on CT. The T2-weighted sequence at the level of the L2-L3 intervertebral disc is used for visceral fat area (VFA), subcutaneous fat area (SFA), and total fat area (TFA). Two radiologists in consensus, calculated the parameters. A total of 250 EC patients (144 low-grade EC, 106 high-grade EC).Sarcopenia was observed in 122 (48.8%) patients, and sarcopenic obesity was found in 82 (32.8%) patients. Although there was an increase in VFA in cases with high-grade EC, there was no significant difference in terms of SFA. Additionally, the frequency of sarcopenia and sarcopenic obesity was higher in cases with high-grade EC. There was no association between sarcopenia and age, histological type, FIGO staging, or comorbidity in the univariate analysis. However, BMI was found to be associated with sarcopenia. Quantitative radiological measurement of sarcopenia, sarcopenic obesity, and body fat composition can be used as novel parameters in the prediction of disease prognosis in endometrial cancer.

A Prospective Observational Analysis of Endometrial Cancer Risk Associated with Thyroid Hormone Dysregulation

This prospective observational study investigated the relationship between thyroid dysfunction and the risk of developing endometrial cancer in a cohort of 100 patients diagnosed with endometrial cancer. Patient data including demographics, medical history, thyroid function tests (T3, T4, TSH levels), and comorbidities (diabetes mellitus and hypertension) were collected. Thyroid dysfunction was defined as T3, T4, or TSH levels outside the reference ranges (T3: 0.8-2.0 ng/mL, T4: 5.1-14.1 ug/dL, TSH: 0.27-4.2 uIU/mL). Logistic regression analyses were performed to evaluate the association between thyroid dysfunction and endometrial cancer risk, adjusting for potential confounders. The study population had a mean age of 55.9 years (range: 35-82 years). Out of 100 patients, 28 (28%) exhibited hypothyroidism (low T3 or T4, or high TSH), and 12 (12%) exhibited hyperthyroidism (high T3 or T4, or low TSH). Univariate logistic regression analysis revealed a significant association between hypothyroidism and endometrial cancer risk (OR = 2.14, 95% CI: 1.22-3.76, p = 0.008). After adjusting for age, diabetes, and hypertension, the multivariate logistic regression analysis showed that hypothyroidism remained an independent risk factor for endometrial cancer (OR = 1.92, 95% CI: 1.07-3.45, p = 0.029). However, the association between hyperthyroidism and endometrial cancer risk was not statistically significant (OR = 1.34, 95% CI: 0.64-2.82, p = 0.439). This study provides evidence for a significant association between hypothyroidism and increased risk of endometrial cancer, independent of age, diabetes, and hypertension. Further research is needed to understand the underlying mechanisms and explore the potential implications for screening and management strategies

Does the most common gynecological cancer have an awareness blind spot? An Israeli preliminary study.

e22540 Background: Our objectives were to assess the awareness of healthy women who present online to endometrial cancer (EC) symptoms and risk factors among the Israeli population. Methods: A survey regarding awareness of EC symptoms and risk factors was published in secure link on popular Israeli feminine social-media groups ( > 20,000 users), for accurate reach. The survey was conducted during May 2023 just before establishing June as Uterine Cancer Awareness Month by IGCS. 1161 healthy women completed the survey voluntarily and anonymously. Results: Thousand-fifty-six women met the survey’s inclusion criteria. About 90% graduated college, all graduated high-school. The respondents were predominantly non-orthodox Jewish. More than quarter had a healthcare background. About two-thirds visit gynecologist at least once a year and about three-quarters had a gynecological examination in the last year. Most respondents were aware of other gynecological cancers, mainly cervical and ovarian cancers. Only about a quarter of the survey population had some awareness of EC symptoms. Nearly half of study population had some idea about signs and symptoms of any gynecological cancer. Regarding EC, more than a quarter were unaware of vaginal bleeding as an EC symptom and about 90% were unaware of any EC risk factors. More than three-quarters were defined as unaware at all. Only about 1% were fully aware. A statistical trend was observed as women older than 45 were more aware than younger. If a symptom occurs, most declared they would visit a gynecologist and only about 8% would refer to their general-practitioner. Conclusions: In our study population, we observed an extremely-low awareness of the most common gynecological cancer in the industrial world (EC) which has easily diagnosed symptoms and risk factors. This striking findings, in a highly-educated and media-exposed group, are a wakeup-call for policymakers and regulators to take further action in order to achieve earlier diagnosis and curative prognosis in EC patients.

Intermittent energy restriction inhibits tumor growth and enhances paclitaxel response in a transgenic mouse model of endometrial cancer

ObjectiveOverweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC. MethodsLkb1fl/flp53fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed. ResultsHFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment. ConclusionIn Lkb1fl/flp53fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women.

«Закольцованы судьбой». Канцерогенные риски у пациенток на фоне синдрома поликистозных яичников

Polycystic ovary syndrome is a proven risk factor for both endometrial hyperplasia and cancer. The article reflects the current paradigm of etiology, pathogenesis and management of patients with endometrial hyperplasia on the background of polycystic ovary syndrome, according to the data of domestic and foreign literature.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

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 &amp;lt; 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 &amp;lt; 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.