Nutrients

Clinical Tolerability and Safety of Ketogenic Diet in Patients with Gynecological Malignancies Undergoing Radiotherapy: Preliminary Results of a Prospective, Randomized, Open-Label Trial (KOMPARC)

Background: Radiotherapy is a common treatment for gynecological malignancies, often accompanied by significant side effects that impact patient nutritional status. The ketogenic diet has been proposed as a complementary nutritional strategy to enhance treatment efficacy, manage side effects, and preserve body composition. However, its safety and feasibility in the oncological setting remain under-investigated. Methods: The KOMPARC study is a prospective, randomized controlled trial evaluating the adherence, safety, and clinical tolerability of a ketogenic diet versus a standard Mediterranean diet in patients with cervical and endometrial cancer undergoing radiotherapy. Before the start of the treatment, patients were randomized to either the ketogenic diet or the standard diet groups. Anthropometric measures, Hand Grip Test, and body composition parameters from bioimpedance analysis were taken before the start of treatment and at the end. Adherence, adverse events, and patient-reported outcomes were monitored throughout the treatment period. Results: A total of 33 patients were enrolled. Adherence rates were comparable between the KD and standard diet groups (46.1% vs. 25.0% interruption rate, p = 0.21). No significant differences were observed in the incidence of gastrointestinal toxicities (p = 0.56), diarrhea (p = 0.81), nausea (p = 0.94), or weight loss (p = 0.24). Both groups experienced significant weight reduction during therapy without differential loss of body cell mass or other body composition parameters. Quality of life assessments indicated varied symptom profiles, with the KD group reporting increased appetite loss and worry about weight. Conclusions: Preliminary findings suggest that the ketogenic diet is a safe and feasible nutritional intervention during radiotherapy for pelvic tumors. These results support further investigation into ketogenic dietary strategies as adjuncts in oncologic care.

Using Genetics to Assess the Role of Acetate in Ischemic Heart Disease, Diabetes, and Sex-Hormone-Related Cancers: A Mendelian Randomization Study

Background: Acetate, a short-chain fatty acid, has gained attention for its contrasting roles, with evidence suggesting it may offer cardiovascular protection but also promote cancer, particularly those involving sex hormones. However, these influences have been scarcely assessed in epidemiological research. Objective: To investigate the relationship between acetate and ischemic heart disease (IHD), diabetes, and cancers related to sex hormones. Methods: Mendelian randomization (MR) was used to assess potential causal effects, selecting genetic variants without linkage disequilibrium (r2 < 0.001) and with genome-wide significance for acetate (p < 5 × 10−8). These variants were applied to large genome-wide association studies (GWAS) for ischemic heart disease (IHD; up to 154,373 cases), diabetes (109,731 cases), and five sex-hormone-related cancers (breast, colorectal, prostate, ovarian, and endometrial cancers, ranging from 8679 to 122,977 cases). We employed various methods for analysis, including penalized inverse variance weighting (pIVW), inverse variance weighting, weighted mode, and weighted median. Results: This study indicates that acetate may be associated with a lower risk of ischemic heart disease (IHD), with an odds ratio (OR) of 0.62 per standard deviation (SD) increase in acetate and a 95% confidence interval (CI) of 0.39 to 0.98. Additionally, acetate was linked to a higher breast cancer risk, with an OR of 1.26 and a 95% CI ranging from 1.08 to 1.46. This association remained robust across multiple sensitivity analyses. Conclusions: Acetate, along with factors that influence its activity, may serve as possible targets for breast cancer treatment and possibly IHD, offering opportunities for new drug development.

Circulating Phylloquinone and the Risk of Four Female-Specific Cancers: A Mendelian Randomization Study

Background: Observational studies have linked vitamin K and cancer, but the causality of this association remains unknown. This Mendelian randomization (MR) study aims to investigate the association between circulating phylloquinone (vitamin K1) levels and four female-specific cancers. Methods: We used four single-nucleotide polymorphisms (SNPs) to instrument phylloquinone, with the reported F-statistic 16.00–28.44 for all variants. SNP–outcome associations were obtained from consortia meta-analyses, UK Biobank, and the FinnGen database (up to 145,257/419,675, 27,446/362,324, 15,181/591,477, and 2211/320,454 cases/controls for breast, ovarian, endometrial, and cervical cancer, respectively). Analyses were conducted using five complementary MR methods including pleiotropy robust approaches. The MR Egger intercept test, MR PRESSO global test and leave-one-out analyses were used to test for and identify pleiotropic variants. Results: The relevance of the instrument was validated by positive control analyses on coagulation factor IX (p = 0.01). However, the main MR analysis and all sensitivity analyses were consistently supportive of a null association between phylloquinone and all four cancers (p > 0.05 for all analyses, across all methods). MR-PRESSO did not detect outlying variants, and there was no evidence of horizontal pleiotropy relating to any cancer outcome (pintercept > 0.26 for all). Conclusions: We found no evidence for an association between genetically predicted circulating phylloquinone levels and the risk of four female-specific cancers.

Possible Prognostic Role of BMI Before Chemotherapy in the Outcomes of Women with Ovarian Cancer

Background/Objectives: Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need to identify modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, both prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conflicting data on the associations of body mass index (BMI) with progression-free survival (PFS) and overall survival (OS) in ovarian cancer patients necessitate further exploration. This study aims to investigate the prognostic role of BMI before chemotherapy in women with ovarian cancer, specifically focusing on PFS and OS. Methods: A retrospective analysis encompassed 1,136 patients diagnosed with ovarian carcinomas between 1995 and 2018. Patients were categorized based on BMI at presentation, and a comprehensive examination of clinicopathological, treatment, and survival data was conducted. Results: In the patient population, normal weight patients (BMI < 25 kg/m2) demonstrated a median PFS of 12.8 months (95% CI 11.7–13.9 months), while overweight/obese patients (BMI ≥ 25 kg/m2) exhibited a significantly longer median PFS of 14.9 months (95% CI 13.6–16.4 months, P = 0.006). No statistically significant difference was noted in median OS between the two BMI groups. Subgroup analysis for different histological subtypes revealed a statistically significant benefit for overweight and obese patients with serous and endometrioid histology (mPFS 12.9 months, 95% CI 11.7–14.0 vs. 15.6 months, 95% CI 13.9–17.3, P = 0.012 and 14.6 months 95% CI 13.7–15.5 vs. 25.6 months, 95% CI 9.5–41.7, P = 0.031, respectively). Additionally, BMI ≥ 25 kg/m2 demonstrated a significant advantage in advanced-stage disease. Conclusions: The study underscores the intricate association between BMI and ovarian cancer prognosis. While a statistically significant difference in progression-free survival was noted between normal weight and overweight/obese patients, with the latter group experiencing a survival benefit, no such difference was observed in overall survival.

Wentilactone A Reverses the NF-κB/ECM1 Signaling-Induced Cisplatin Resistance through Inhibition of IKK/IκB in Ovarian Cancer Cells

Wentilactone A (WA) is a tetranorditerpenoid isolated from marine algae. We previously found that WA inhibited cancer cell proliferation with little toxicity. In this study, we show that high expression of extracellular matrix protein-1 (ECM1) promotes cancer cell cisplatin resistance, and the secreted ECM1 activates normal fibroblasts (NFs) to transform cells with characteristics of cancer-associated fibroblasts (CAFs). Transcription of the ECM1 gene is regulated largely by NF-κB through EP881C/T-EP266C binding sites. WA supresses the phosphorylation of NF-κB through inhibition of the upstream IKK/IκB phoshorylation to block the expression of ECM1, which reverses the cisplatin-induced activation of NF-κB/ECM1. On the contrary, cisplatin facilitates phosphorylation of NF-κB to enhance the expression of ECM1. These results highlight ECM1 as a potential target for treatment of cisplatin-resistant cancers associated with the ECM1 activated signaling. In addition, WA reverses cisplatin resistance by targeting both tumor cells and the tumor microenvironment through IKK/IκB/NF-κB signaling to reduce the expression of the ECM1 protein.

Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer

Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer.

Eating Behaviors and Physical Activity versus the Big Five Personality Traits in Women with a Hereditary Predisposition to Breast or Ovarian Cancer

The Big Five personality traits—neuroticism, extroversion, openness to experience, agreeableness, and conscientiousness—represent continuous, individual features that affect a number of vital health aspects, including morbidity, self-reported health status, or lifestyle. The aim of this study was to analyze the relationship between the eating behaviors and engagement in physical activity of women with a hereditary predisposition to breast or ovarian cancer and the Big Five personality traits. A total of 357 women, participants of ‘The National Program for Families With Genetic/Familial High Risk for Cancer’, were included in the study. In the healthy group, the following statistically significant predictors were found in variables: agreeableness—meal frequency (β = 0.151; p = 0.030); neuroticism—consumption of fruits and vegetables (β = −0.177; p = 0.016) and cereal products (β = −0.223; p = 0.002); openness to experience—consumption of plant-based fats (β = 0.141; p = 0.034) and physical activity (β = 0.153; p = 0.021). In the cancer group, the frequency of dairy consumption (β = 0.286; p = 0.003) and physical activity (β = 0.370; p = 0.000) were found to be statistically significant predictors for the openness to experience variable. Neuroticism is associated with less frequent consumption of fresh fruits and vegetables as well as cereal products. Openness to experience was more often linked with a higher frequency of dairy consumption, plant-based fats, and physical activity. Women with breast or ovarian cancer and a higher openness to experience consumed dairy and engaged in physical activity more often than their peers with the remaining personality traits.

Vitamins in Gynecologic Malignancies

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

Role of Fisetin in Selected Malignant Neoplasms in Women

A promising therapeutic window and cost-effectiveness are just two of the potential advantages of using naturally derived drugs. Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a natural flavonoid of the flavonol group, commonly found in fruit and vegetables. In recent years, fisetin has gained wide attention across the scientific community because of its broad spectrum of pharmacological properties, including cytotoxic activity against most abundant cancers. By stimulating or inhibiting selected molecular targets or biochemical processes, fisetin could affect the reduction of metastasis or cancer progression, which indicates its chemotherapeutic or chemopreventive role. In this review, we have summarized the results of studies on the anticancer effects of fisetin on selected female malignancies, both in in vitro and in vivo tests, i.e., breast, cervical, and ovarian cancer, published over the past two decades. Until now, no article dedicated exclusively to the action of fisetin on female malignancies has appeared. This review also describes a growing number of nanodelivery systems designed to improve the bioavailability and solubility of this natural compound. The reported low toxicity and activity of fisetin on cancer cells indicate its valuable potential, but large-scale clinical trials are urgently needed to assess real chemotherapeutic efficacy of this flavonoid.

Study of Serum Copper and Zinc Levels and Serum Cu/Zn Ratio among Polish Women with Endometrial Cancer

Background: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed. Methods: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer. Results: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 μg/L vs. 1176.42 μg/L, p < 0.001; Zn: 707.05 μg/L vs. 901.67 μg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001). Conclusion: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

Unrestricted Ketogenic Diet Feeding Enhances Epithelial Ovarian Cancer Growth In Vivo

The ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syngeneic with C57Bl/6J mouse strain and transfected with luciferase (ID8-luc), were injectedand monitored for tumor development. Female mice were fed either a strict KD, a high fat/low carbohydrate (HF/LC) diet, or a low fat/high carbohydrate (LF/HC) diet (n = 10 mice per group) ad libitum. EOC tumor growth was monitored weekly, and tumor burden was determined based on luciferase fluorescence (photons/second). At the endpoint (42 days), tumors were collected and processed for RNA sequencing. Plasma and tumor metabolites were evaluated using LC-MS. The KD-fed mice exhibited a statistically significant increase in tumor progression in comparison to the HF/LC- and LF/HC-fed groups (9.1 vs. 2.0 vs. 3.1-fold, respectively, p < 0.001). The EOC tumors of the KD-fed mice exhibited significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid metabolism pathways based on the RNA sequencing analysis when compared to the LF/HC- and HF/LC-fed mice. Thus, unrestricted KD diet enhanced tumor progression in our mouse EOC model. KD was associated with the upregulation of fatty acid metabolism and regulation pathways, as well as enrichment of fatty acid and glutamine metabolites.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Associations of Dietary Intakes with Gynecological Cancers: Findings from a Cross-Sectional Study

Background: Gynecological cancers, including cervical cancer, ovarian cancer and endometrial cancer are leading causes of cancer-related death in women worldwide. Diet plays an important role in cancer development, which is widely accepted. However, the associations between dietary intakes and gynecological cancers remain unclear. Methods: A total of 12,437 women aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007–2016, were included in this study. The relationships between 30 dietary factors (4 macronutrients, 15 vitamins, 9 minerals, caffeine and alcohol) and gynecological cancers were assessed. Results: We observed negative correlations of intakes of phosphorus (odds ratio (OR), 95% confidence interval (CI); 0.998 (0.996, 0.999), p = 0.002) with cervical cancer, and intakes of vitamin B12 (0.812 (0.714, 0.925), p = 0.002), phosphorus (0.997 (0.996, 0.999), p < 0.001) and alcohol (0.971 (0.950, 0.992), p = 0.009) with endometrial cancer. The data showed positive associations of intake of caffeine (1.002 (1.001, 1.003), p = 0.003) with cervical cancer, and intake of copper (2.754 (1.313, 5.778), p = 0.009) with endometrial cancer. In addition, we found potential negative correlations between intake of vitamin B1 (p = 0.025) and cervical cancer; zinc (p = 0.048) and ovarian cancer; and potassium (p = 0.032) and endometrial cancer. Potential positive associations were found between intake of calcium and cervical cancer (p = 0.026) and endometrial cancer (p = 0.034), and between sodium (p = 0.042) and endometrial cancer. Intakes of protein, total sugars, total fat, cholesterol, vitamin A, alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, vitamin B2, niacin, vitamin B6, food folate, vitamin C, vitamin D, vitamin E, vitamin K, magnesium, iron and selenium showed no relationship with gynecological cancers (p > 0.05). Conclusions: Specific dietary factors were associated with gynecological cancers. More epidemiological studies are needed to validate our results.

Dietary Factors and Endometrial Cancer Risk: A Mendelian Randomization Study

Given the strong association between obesity and endometrial cancer risk, dietary factors may play an important role in the development of this cancer. However, observational studies of micro- and macronutrients and their role in endometrial cancer risk have been inconsistent. Clarifying these relationships are important to develop nutritional recommendations for cancer prevention. We performed two-sample Mendelian randomization (MR) to investigate the effects of circulating levels of 15 micronutrients (vitamin A (retinol), folate, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, β-carotene, calcium, copper, iron, magnesium, phosphorus, selenium, and zinc) as well as corrected relative macronutrient intake (protein, carbohydrate, sugar and fat) on risks of endometrial cancer and its subtypes (endometrioid and non-endometrioid histologies). Genetically predicted vitamin C levels were found to be strongly associated with endometrial cancer risk. There was some evidence that genetically predicted relative intake of macronutrients (carbohydrate, sugar and fat) affects endometrial cancer risk. No other significant association were observed. Conclusions: In summary, these findings suggest that vitamin C and macronutrients influence endometrial cancer risk but further investigation is required.

The Associations between Metalloestrogens, GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer

Background: The incidence of endometrial cancer (EC) is still rising. Numerous risk factors including patient characteristics and molecular instability have been identified for EC. The presence of specific molecular markers allows specific diagnostic and prognostic approaches. Several single nucleotide polymorphisms (SNPs) have been identified to influence endometrial cancer risk. Metalloestrogens are metal ions which can mimic estrogen activity; however, their role in uterine pathologies remains unknown. This study aimed to investigate total blood trace elements levels and evaluate the distribution of selected genotypes in GSTP1 and SLC11A2 genes. Methods: This retrospective case-control analysis was carried out in peripheral blood samples of 110 women with endometrial cancer (EC; n = 21), uterine fibroma (n = 25), endometrial polyp (n = 48), and normal endometrium (n = 16). Analysis included measurement of metals and phosphor in serum, and of genetic polymorphisms in GST (rs1695) and SLC11A2 (rs224589) in DNA from white blood cells. Serum trace elements were measured using ICP-OES spectrometry. SNPs were identified using Taq Man real-time PCR genotyping assays. Results: The study confirmed higher age (OR 2.19, 95% CI 1.69–2.24), post-menopausal status (OR 1.89, 95% CI 1.36–1.94), and diabetes type 2 (OR 1.54; 95% CI 0.97–1.72) as independent risk factors for EC. We also found a high level of Cd (OR 1.49; 95% CI 1.31–1.63) and a low level of Co (OR 0.76; 95% CI 0.53–0.59) to be independent risk factors of EC. None of the tested polymorphisms of GSTP1 and SLC11A2 were associated with EC risk. However, high Cd (OR 1.21, 95% CI 1.15–1.29) and Ni (OR 1.07, 95% CI 1.05–1.18) serum levels were significantly associated with a SLC1A2 TG genotype, and high Cd levels with GSTP1 (OR 1.05, 95% CI 1.01–1.13).

Evaluation of the Concentration of Selected Elements in Patients with Cancer of the Reproductive Organs with Respect to Treatment Stage—Preliminary Study

(1) Background: The aim of this study was to assess the concentrations of selected elements in female patients with cancer of the reproductive organs, taking into account the stage of treatment. (2) Methods: The study sample consisted of 51 patients with advanced endometrial cancer and ovarian cancer, undergoing chemotherapy. The median age of the studied patients with endometrial cancer was 66.0 years (IQR: from 60.75 to 70.25), and with ovarian cancer―60.0 years (IQR: from 49.0 to 64.0). Each of the qualified women, after consent to participate in the study, had her blood drawn several times (before surgery, the first course of chemotherapy, the third course of chemotherapy, and the sixth course of chemotherapy) in order to determine serum levels of macro- and micronutrients (Na, Mg, Ca, Zn, P, Cu, Fe, Cd, Ni, and Sr). (3) Results: In the study group of patients with cancer of the reproductive tract, the concentrations of iron (<0.001), magnesium (0.038), sodium (0.014), and nickel (0.037) varied significantly over the course of the study. The analysis showed that the interaction between the stage of chemotherapy and the type of cancer had an effect on the concentrations of magnesium and cadmium (p < 0.05). (4) Conclusions: In the studied group of patients with ovarian and endometrial cancer, the applied chemotherapy significantly changed the concentrations of Fe, Na, and Ni, regardless of the type of tumor. Changes in Mg and Cd concentrations resulted from the interaction between the stage of chemotherapy and the type of cancer. The results of serum concentrations of selected elements in women with cancer of the reproductive organs may help understand the physiological changes resulting from the applied chemotherapy.

An Assessment of Serum Selenium Concentration in Women with Endometrial Cancer

Background: Numerous studies have shown a relationship between low serum selenium levels and an increased risk of developing cancer. Methods: A total of 306 women participated in the study: 153 patients diagnosed with endometrial cancer and 153 healthy women who were matched, in terms of birth year (+/−3 years), to the patients from the study group. The quantitative measurement of selenium content in the collected blood samples was performed using a mass spectrometer with excitation in inductively coupled plasma. In order to determine the relationship between the risk factors and the incidence of endometrial cancer, analyses based on single- and multi-factor conditional logistic regression models were performed. Results: The mean concentration of selenium was lower in patients with endometrial cancer than in healthy controls (60.63 µg/L (0.77 µmol/L) vs. 78.74 µg/L (0.99 µmol/L), respectively). When compared in quartiles, a significant association of lower selenium concentration with the incidence of endometrial cancer was recorded. The highest OR was observed in the first and second quartiles (OR-22.0, p-value < 0.001; medium selenium level 46.95 µg/L (0.59 µmol/L), and OR-5.94; p-value < 0.001; medium selenium level 63.60 µg/L (0.80 µmol/L), respectively). Conclusion: A strong correlation between the level of selenium in the blood serum and the risk of endometrial cancer indicates that patients with low levels should be a candidate group requiring appropriate preventive examinations. Further research on a larger group of patients is required.

Pretreatment Nutritional Status in Combination with Inflammation Affects Chemotherapy Interruption in Women with Ovarian, Fallopian Tube, and Peritoneal Cancer

Background: Discontinuing chemotherapy worsens cancer prognosis. This study aimed to investigate the relationship between nutritional status at the start of chemotherapy and chemotherapy discontinuation in patients with ovarian, fallopian tube, and primary peritoneal cancer. Methods: This was a retrospective cohort study. One hundred and forty-six patients to whom weekly paclitaxel and carboplatin were administered as postoperative chemotherapy were included. Six courses in 21-day cycles were defined as complete treatment. As nutritional indicators, body mass index, weight change rate, serum albumin, total lymphocyte count, prognostic nutritional index, and C-reactive protein-to-albumin ratio (CAR) were compared between complete and incomplete treatment groups. Patients were divided into two groups according to CAR. The number of chemotherapy cycles was compared between these two groups. A Cox proportional hazard model was used for covariate adjustment. Results: Several indicators differed between complete and incomplete treatment groups, and among the indicators, CAR had the highest discriminatory ability. The number of chemotherapy cycles was shorter in the high CAR group than in the low CAR group. A high CAR was associated with chemotherapy interruption even after adjusting for covariates. Conclusion: Based on CAR, nutritional status before chemotherapy is suggested to be associated with the risk of chemotherapy discontinuation.

Plant-Based Diets and Ovarian Cancer Risk

Objective: To assess the relationship between adherence to various plant-based diets, as measured by overall, healthy, and unhealthy plant-based diet indices (PDI, hPDI, uPDI), and ovarian cancer risk. Methods: We obtained data on 1031 cases of ovarian cancer and 2411 controls from a case-control study conducted in Italy. PDI, hPDI, and uPDI were calculated using data from a validated food frequency questionnaire. We used logistic regression to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of ovarian cancer for PDI, hPDI, and uPDI, adjusting for several possible confounders. Results: PDI and hPDI were inversely related to ovarian cancer risk (OR = 0.70 for the fourth compared to the first quartile, 95% CI: 0.55–0.89, and OR = 0.67, 95% CI: 0.53–0.84, respectively). On the other hand, a higher uPDI was related to a higher risk of ovarian cancer (OR = 1.78, 95% CI: 1.40–2.28). The estimates for a 5-point increment in the indices were 0.88 (95% CI: 0.81–0.95) for PDI, 0.90 (95% CI: 0.83–0.96) for hPDI, and 1.15 (95% CI: 1.07–1.23) for uPDI. Consistent associations for the three indices were observed across strata of age, family history of breast/ovarian cancer, educational level, parity, oral contraceptives use, and menopausal status. Conclusions: Plant-based diets favorably influence ovarian cancer risk; plant-based diets characterized by a high intake of unhealthy plant foods are linked to an increased risk. Promoting diets rich in healthy plant foods could support the reduction of ovarian cancer risk.

Butyrate as a Potential Modulator in Gynecological Disease Progression

This review investigates the therapeutic potential of butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, in the prevention and treatment of various gynecological diseases, including polycystic ovary syndrome (PCOS), endometriosis, and gynecologic cancers like cervical and ovarian cancer. These conditions often pose treatment challenges, with conventional therapies offering limited and temporary relief, significant side effects, and a risk of recurrence. Emerging evidence highlights butyrate’s unique biological activities, particularly its role as a histone deacetylase (HDAC) inhibitor, which allows it to modulate gene expression, immune responses, and inflammation. In PCOS, butyrate aids in restoring hormonal balance, enhancing insulin sensitivity, and reducing chronic inflammation. For endometriosis, butyrate appears to suppress immune dysregulation and minimize lesion proliferation. Additionally, in cervical and ovarian cancers, butyrate demonstrates anticancer effects through mechanisms such as cell cycle arrest, apoptosis induction, and suppression of tumor progression. Dietary interventions, particularly high-fiber and Mediterranean diets, that increase butyrate production are proposed as complementary approaches, supporting natural microbiota modulation to enhance therapeutic outcomes. However, butyrate’s short half-life limits its clinical application, spurring interest in butyrate analogs and probiotics to maintain stable levels and extend its benefits. This review consolidates current findings on butyrate’s multifaceted impact across gynecological health, highlighting the potential for microbiota-centered therapies in advancing treatment strategies and improving women’s reproductive health.

Antimicrobial and Anticancer Activities of Lactiplantibacillus plantarum Probio87 Isolated from Human Breast Milk

Background/Objectives: This study evaluated the in vitro probiotic potential of Lactiplantibacillus plantarum Probio87 (Probio87), focusing on its physiological robustness, safety, antimicrobial properties, and anticancer activity, with relevance to vaginal and cervical health. Methods: Tests included acid and bile salt tolerance, mucin adhesion, and carbohydrate utilization. Prebiotic preferences were assessed using FOS, GOS, and inulin. Antibiotic susceptibility was evaluated per EFSA standards. Antimicrobial activity of the cell-free supernatant (CFS) was tested against Staphylococcus aureus, Escherichia coli, and Candida species. Effects on Lactobacillus iners and L. crispatus were analyzed. Anticancer properties were assessed in HeLa, CaSki (HPV-positive), and C-33A (HPV-negative) cervical cancer cell lines through proliferation, apoptosis, angiogenesis, and cell cycle assays. Results: Probio87 showed strong acid and bile tolerance, efficient mucin adhesion, and broad carbohydrate utilization, favoring short-chain prebiotics like FOS and GOS over inulin. It met EFSA antibiotic safety standards. The CFS exhibited potent antimicrobial activity, including complete inhibition of Candida albicans. Probio87 selectively inhibited L. iners without affecting L. crispatus, indicating positive modulation of vaginal microbiota. In cervical cancer cells, the CFS significantly reduced proliferation and angiogenesis markers (p < 0.05), and induced apoptosis and cell cycle arrest in HPV-positive cells, with minimal effects on HPV-negative C-33A cells. Conclusions: Probio87 demonstrates strong probiotic potential, with safe, selective antimicrobial and anticancer effects. Its ability to modulate key microbial and cancer-related pathways supports its application in functional foods or therapeutic strategies for vaginal and cervical health.

A Diet Lacking Selenium, but Not Zinc, Copper or Manganese, Induces Anticancer Activity in Mice with Metastatic Cancers

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53−/− murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers.

Nature of the Association between Rheumatoid Arthritis and Cervical Cancer and Its Potential Therapeutic Implications

It is now established that patients with rheumatoid arthritis (RA) have an increased risk of developing cervical cancer (CC) or its precursor, cervical intraepithelial neoplasia (CIN). However, the underlying mechanisms of this association have not been elucidated. RA is characterized by unresolved chronic inflammation. It is suggested that human papillomavirus (HPV) infection in RA patients exacerbates inflammation, increasing the risk of CC. The tumor microenvironment in RA patients with CC is also marked by chronic inflammation, which aggravates the manifestations of both conditions. Gut and vaginal dysbiosis are also considered potential mechanisms that contribute to the chronic inflammation and aggravation of RA and CC manifestations. Numerous clinical and pre-clinical studies have demonstrated the beneficial effects of various nutritional approaches to attenuate chronic inflammation, including polyunsaturated fatty acids and their derivatives, specialized pro-resolving mediators (SPMs), probiotics, prebiotics, and certain diets. We believe that successful resolution of chronic inflammation and correction of dysbiosis, in combination with current anti-RA and anti-CC therapies, is a promising therapeutic approach for RA and CC. This approach could also reduce the risk of CC development in HPV-infected RA patients.

Diabetes Risk Reduction Diet and Endometrial Cancer Risk

Diabetes increases endometrial cancer risk. We investigated the role of a diabetes risk reduction diet (DRRD) on the risk of endometrial cancer using data from a multicentric, Italian hospital-based case–control study (1992–2006) enrolling 454 histologically confirmed cases of endometrial cancer and 908 controls matched by age and center. We derived a DRRD score assigning higher scores for higher intakes of cereal fiber, fruit, coffee, polyunsaturated:saturated fatty acid ratio, and nuts and for lower glycemic load and lower intakes of red/processed meat and sugar-sweetened beverages/fruit juices. The odds ratios (OR) of endometrial cancer according to the DRRD score were derived by multiple conditional logistic regression models. The OR for high (DRRD score >24, i.e., third tertile) versus medium–low adherence to the DRRD was 0.73 (95% confidence interval, CI, 0.55–0.97). Similar results were observed after the exclusion of diabetic women (OR 0.75; 95% CI, 0.56–1.00) and allowance for total vegetable consumption (OR 0.80; 95% CI, 0.60–1.07). Inverse associations were observed in most of the analyzed subgroups. The OR for high DRRD combined with high vegetable consumption was 0.45 (95% CI, 0.28–0.73). Our results suggest that diets able to reduce diabetes risk may also reduce endometrial cancer risk. High vegetable consumption combined with high adherence to the DRRD may provide additional benefit in endometrial cancer prevention.

Purine Intake and All-Cause Mortality in Ovarian Cancer: Results from a Prospective Cohort Study

Background: Current biological evidence suggests that purine involvement in purine metabolism may contribute to the development and progression of ovarian cancer (OC), but the epidemiological association is currently unknown. Methods: A total of 703 newly diagnosed patients with OC aged 18–79 years were included in this prospective cohort study. Utilizing a verified food-frequency questionnaire, the participants’ dietary consumption was gathered. Using medical records and ongoing follow-up, the deaths up until 31 March 2021 were determined. To assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of purine intake with OC mortality, Cox proportional-hazard models were utilized. Results: During the median follow-up of 31 months (interquartile: 20–47 months), 130 deaths occurred. We observed an improved survival for the highest tercile of total purine intake compared with the lowest tercile (HR = 0.39, 95% CI = 0.19–0.80; p trend < 0.05), and this protective association was mainly attributed to xanthine intake (HR = 0.52, 95% CI = 0.29–0.94, p trend < 0.05). Additionally, we observed a curving relationship in which OC mortality decreased with total purine intake, and the magnitude of the decrease was negatively correlated with intake (p non-linear < 0.05). Significant inverse associations were also observed in subgroup analyses and sensitivity analyses according to demographic and clinical characteristics. Moreover, we observed that xanthine intake and hypoxanthine intake had a multiplicative interaction with ER and PR expression (p < 0.05), respectively. Conclusion: A high total purine and xanthine intake was linked to a lower risk of OC mortality. Further clarification of these findings is warranted.

An Assessment of Serum Selenium Concentration in Women with Ovarian Cancer

Background: Available studies on the effect of serum selenium levels on the risk of malignancies show some conflicting results. In this study, we investigated the correlation between serum selenium levels and ovarian cancer occurrence. Methods: 314 women (157 diseased patients and 157 healthy ones) matched in terms of age and BMI were included in the study. The measurements of selenium in the collected blood samples were performed using an ICP mass spectrometer. Univariable and multivariable analyzes were performed to determine the relationship between the factors under the study and the occurrence of ovarian cancer. Results: The mean concentration of selenium was lower among diseased ones than among controls (53.31 μg/L vs. 78.99 μg/L). A decrease in selenium concentration was noticed with the advancement of ovarian cancer. In univariable and multivariable analyzes, a clear relationship between low selenium concentration and the occurrence of ovarian cancer was found (35.3 (95% CI: 11.2–111; p < 0.001) and 45.8 (95% CI: 12.8–164; p < 0.001)). Conclusion: The studied patients with ovarian cancer are characterized by statistically significant lower serum selenium levels than patients from the control group. Among the study group, a decrease in selenium concentration was observed with an increase in the FIGO stage. The determination of the role of selenium as a prophylactic factor in ovarian cancer requires further prospective studies.

Association between Cervical Cancer and Dietary Patterns in Colombia

Cervical cancer is a global public health problem. It is the second leading cause of death among women of childbearing age worldwide. Several factors, including diet, have been shown to influence the risk of persistent HPV infection and tumor progression. This paper determines the relationship between dietary patterns and cervical cancer. It is an ecological study of multiple groups, based on two national sources: the High-Cost Account and the National Survey of Nutritional Situation of Colombia of 2015. The population consisted of 3472 women aged 35 to 64. The incidence of cervical cancer was used as the dependent variable while the independent variables included food consumption according to established patterns, area of residence, age, physical activity, and BMI, among other variables. The statistical analysis performed through associations between variables was evaluated by multiple linear regression using R2. 38.9% of the evaluated population belonged to the first quartile of wealth, and 76.5% resided in the municipal capital. The incidence of cervical cancer in Colombia was associated with being affiliated to a state-subsidized health regime and having diabetes mellitus. A conservative eating pattern, as well as belonging to a rural area, are evidenced as protective factors. These results invite the need to encourage public policies and promote healthy lifestyles.

Evaluating Preconception Health and Behaviour Change in Australian Women Planning a Pregnancy: The OptimalMe Program, a Digital Healthy Lifestyle Intervention with Remotely Delivered Coaching

OptimalMe is a digital healthy lifestyle intervention for women planning a pregnancy, with remotely delivered coaching. This follow-up study of Australian women, stratified by coaching delivery mode (phone vs. videoconferencing), assessed alignment to preconception care guidelines and self-reported behaviour change. Overall, 298 women enrolled with a mean (SD) age of 31.8 (4.3) years and mean BMI of 25.7 (6.1) kg/m2. Suboptimal preconception behaviours were reported at baseline, including alcohol consumption (57.2%), infrequent weighing (37.2%) and incomplete cervical cancer screening (15.8%) and prenatal supplementation (38.5). At follow-up (4.5 months) (n = 217), a statistically significant shift towards desired behaviours was reported for alcohol consumption (z = −2.6045, p = 0.00932), preconception supplementation (z = −2.7288, p = 0.00634) and frequent weight monitoring (z = −5.2911, p < 0.00001). An insignificant shift towards adherence to cervical cancer screening (z = −1.8679, p = 0.06148) was observed, with a positive trend towards adherence. Results indicate that women who are actively planning a pregnancy require support to optimise health and lifestyle in preparation for pregnancy and general health and lifestyle improvement. Women demonstrated improvement in lifestyle behaviours and self-monitoring, indicating the uptake of low-intensity, non-prescriptive information provision. Supporting the provision of knowledge-enhancing tools and general healthy lifestyle information combines with skilled health coaching as an effective method for behaviour change and self-management. OptimalMe also shows significant improvements in rates of healthcare engagement, which suggests coaching-based digital health interventions may decrease women’s barriers for preconception care and improve engagement in clinical settings.

Diabetes-Related Dietary Patterns and Endometrial Cancer Risk and Survival in the European Prospective Investigation into Cancer and Nutrition Study

Background/Objectives: Endometrial cancer (EC)’s major risk factors include obesity and diabetes, both strongly related with lifestyle choices and dietary factors. Our study aimed to evaluate the relationship between diabetes-related dietary patterns, EC risk, and survival in a population of middle-aged European women. Methods: A total of 285,418 female participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included in the analysis. After a mean time of 10.6 years of follow-up, 1955 incident EC cases were registered; of those, 133 women died from EC. The Empirical Dietary Index for Insulin Resistance (EDIR), the Empirical Dietary Index for Hyperinsulinemia (EDIH), and the Diabetes Risk Reduction Diet (DRRD), were estimated from dietary information collected at baseline from EPIC participants. Cox proportional hazards regression models were used to evaluate the association between the dietary patterns and EC risk, using hazard ratios (HR), 95% confidence intervals (CI), and adjusting for relevant confounders. Cox and Fine–Gray models were used to assess the association with overall and EC-specific mortality, respectively. Results: Higher adherence to EDIR was associated with an increased risk of EC, multivariable HR for T3vsT1 were 1.17 (95% CI = 1.04 to1.31). However, when BMI was included in the models, these associations became weaker and no longer statistically significant. No associations were observed in relation to adherence to EDIH, DRRD, and EC risk. No associations were found in relation to diabetes-related dietary patterns and mortality. Conclusions: This study highlights the potential role of diabetes related dietary patterns and EC etiology and prevention. Further studies are warranted to better understand the role of etiology-derived dietary patterns and disease prevention and prognosis.

Serum 25-Hydroxyvitamin D and Cancer Risk: A Systematic Review of Mendelian Randomization Studies

Epidemiological studies suggest that higher serum 25-hydroxyvitamin D is associated with lower risk for several cancers, including breast, prostate, colorectal, and lung cancers. To mitigate confounding, genetic instrumental variables (IVs) have been used to estimate causal associations between 25-hydroxivtamin D and cancer risk via Mendelian randomization (MR). We provide a systematic review of 31 MR studies concerning 25-hydroxyvitamin D and cancer incidence and mortality identified from biomedical databases. MR analyses were conducted almost exclusively in European-ancestry populations and identified no statistically significant associations between higher genetically predicted 25-hydroxyvitamin D and lower risk for total cancer or colorectal, breast, prostate, lung, or pancreatic cancers. In recent studies including ≥80 genetic IVs for 25-hydroxyvitamin D, null associations were reported for total cancer (odds ratio [95% confidence interval] per 1-standard deviation increase: 0.98 [0.93–1.04]), breast (1.00 [0.98–1.02]), colorectal (0.97 [0.88–1.07]), prostate (0.99 [0.98–1.01]), and lung cancer (1.00 [0.93–1.03]). A protective association was observed for ovarian cancer in the Ovarian Cancer Association Consortium (0.78 [0.63–0.96] per 20 nmol/L increase, p-trend = 0.03), but not in the UK Biobank (1.10 [0.80–1.51]). Null associations were reported for other tumor sites (bladder, endometrium, uterus, esophagus, oral cavity and pharynx, kidney, liver, thyroid, or neural cells). An inconsistent protective association for cancer-specific mortality was also observed. Results from MR analyses do not support causal associations between 25-hydroxyvitamin D and risk for cancer incidence or mortality. Studies including non-White populations may be valuable to understand low 25-hydroxyvitamin D as a modifiable risk factor in populations with a higher risk of common cancers, including African ancestry individuals.

Association among Vitamin D, Retinoic Acid-Related Orphan Receptors, and Vitamin D Hydroxyderivatives in Ovarian Cancer

Vitamin D and its derivatives, acting via the vitamin D receptor (VDR) and retinoic acid-related orphan receptors γ and α (RORγ and RORα), show anticancer properties. Since pathological conditions are characterized by disturbances in the expression of these receptors, in this study, we investigated their expression in ovarian cancers (OCs), as well as explored the phenotypic effects of vitamin D hydroxyderivatives and RORγ/α agonists on OC cells. The VDR and RORγ showed both a nuclear and a cytoplasmic location, and their expression levels were found to be reduced in the primary and metastatic OCs in comparison to normal ovarian epithelium, as well as correlated to the tumor grade. This reduction in VDR and RORγ expression correlated with a shorter overall disease-free survival. VDR, RORγ, and RORα were also detected in SKOV-3 and OVCAR-3 cell lines with increased expression in the latter line. 20-Hydroxy-lumisterol3 (20(OH)L3) and synthetic RORα/RORγ agonist SR1078 inhibited proliferation only in the OVCAR-3 line, while 20-hydroxyvitamin-D3 (20(OH)D3) only inhibited SKOV-3 cell proliferation. 1,25(OH)2D3, 20(OH)L3, and SR1078, but not 20(OH)D3, inhibited spheroid formation in SKOV-3 cells. In summary, decreases in VDR, RORγ, and RORα expression correlated with an unfavorable outcome for OC, and compounds targeting these receptors had a context-dependent anti-tumor activity in vitro. We conclude that VDR and RORγ expression can be used in the diagnosis and prognosis of OC and suggest their ligands as potential candidates for OC therapy.

Discharging Women with Advanced Ovarian Cancer on Home Parenteral Nutrition: Making and Implementing the Decision

Increasingly, patients with advanced ovarian cancer in bowel obstruction are receiving home parenteral nutrition (HPN). Little is known about making and implementing the decision. This study explored the decision-making process for HPN and investigated the barriers and facilitators to implementation. This was a qualitative study underpinned by phenomenology involving 93 longitudinal in-depth interviews with 20 patients, their relatives and healthcare professionals, over 15 months. Participants were interviewed a maximum of four times. Interview transcripts were analysed thematically as per the techniques of Van Manen. We found variance between oncologists and patients regarding ownership of the HPN decision. The oncologists believed they were engaging in a shared decision-making process. However, patients felt that the decision was oncologist-driven. Nevertheless, they were content to have the treatment, when viewing the choice as either HPN or death. In implementing the decision, the principal mutable barrier to a timely discharge was communication difficulties across professional disciplines and organisations. Facilitators included developing a single point-of-contact between organisations, improving communication and implementing standardised processes. Oncologists and patients differ in their perceptions of how treatment decisions are made. Although patients are satisfied with the process, it might be beneficial for healthcare professionals to check patients’ understanding of treatment.

Nutrients-Rich Food Index Scores and the Overall Survival of Ovarian Cancer Patients: Results from the Ovarian Cancer Follow-Up Study, a Prospective Cohort Study

Background: The nutrients-rich food (NRF) index provides a score of diet quality. Although high diet quality is associated with survival of ovarian cancer (OC), the associations between NRF index scores and OC survival remain unevaluated. Methods: The prospective cohort study enrolled 703 women with newly diagnosed epithelial OC to assess the correlations between NRF index scores and overall survival (OS) in OC patients. Dietary consumption was evaluated through a food frequency questionnaire and diet quality was calculated based on NRF index scores, including three limited nutrients and six (NRF6.3), nine (NRF9.3), or eleven (NRF11.3) benefit nutrients. All-cause deaths were ascertained through medical records combined with active follow-up. Immunohistochemistry (IHC) analyses were conducted to evaluate the expression of IHC indicators (including Estrogen Receptor, Progesterone Receptor, p53, Vimentin, and Wilms’ tumor 1), which were identified by two independent pathologists. The Cox proportional hazards regression models were applied for estimating the hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we performed the penalized cubic splines model to assess the curvilinear associations of NRF index scores with OC survival. Results: During the median follow-up of 37.17 (interquartile: 24.73–50.17) months, 130 deaths were documented. Compared to the lowest tertiles, the highest tertile of index scores [NRF9.3 (HR = 0.63, 95% CI = 0.41–0.95), NRF6.3 (HR = 0.59, 95% CI = 0.39–0.89), and NRF11.3 (HR = 0.57, 95% CI = 0.38–0.87)] were correlated to better OS, showing an obvious linear trend (all p trend < 0.05). Interestingly, the curvilinear association between the NRF6.3 index score and OC survival was also observed (p non-linear < 0.05). Subgroup analyses, stratified by clinical, demographic, and IHC features, showed similar risk associations as the unstratified results. Furthermore, there were significant multiplicative interactions between NRF index scores and Progestogen Receptors as well as Wilms’ tumor 1 expressions (all p interaction < 0.05). Conclusions: Higher NRF index scores were associated with an improved OS in OC patients.

Eliminating Digestive Irregularities Caused by Late Effects: A Pilot Study of an Innovative Culinary Nutrition Intervention for Reducing Gastrointestinal Toxicity in Gynecologic Cancer Patients Who Have Undergone Pelvic Radiotherapy

Background/Objectives: Pelvic radiotherapy (RT) improves survival in gynecologic cancer patients but often results in gastrointestinal (GI) toxicity, affecting quality of life. Standard nutrition guidance lacks specificity for these survivors, complicating dietary choices. To address this gap, the EDIBLE intervention was developed to offer structured dietary self-management skills to alleviate RT-induced GI toxicity. Methods: We conducted a single-arm mixed-methods pilot of the EDIBLE intervention among post-treatment gynecologic cancer survivors to assess its feasibility, acceptability, and preliminary effects on GI symptoms, knowledge, and self-efficacy, with measures at baseline (T1), post-intervention (T2), and after 3 months (T3). Results: Qualitative interviews supported strong perceptions of intervention feasibility; however, the recruitment (32%) and retention (72%) rates were modest, indicating that alternate formats for program delivery may be needed to make it more accessible. The acceptability of the EDIBLE intervention garnered especially high ratings on measures of satisfaction and utility, with program improvements largely rallying around a desire for increased in-class sessions and program expansion. Statistically significant improvements were observed at the three-month mark (T3), such as enhanced confidence in culinary practices, increased knowledge and skills with regard to managing GI side effects, and improvements in bowel and GI symptoms. Conclusions: The results suggest EDIBLE is acceptable, improving GI symptoms and self-efficacy; however, moderate recruitment rates indicate refinement is needed. A randomized control trial and cost-effectiveness analysis is needed to confirm effectiveness and scalability.

Association between Different Types of Tea Consumption and Risk of Gynecologic Cancer: A Meta-Analysis of Cohort Studies

Plenty of studies have shown that tea has an effect of inhibiting gynecologic tumors. However, there still remained controversy of the association between tea and gynecologic tumors in epidemiological studies. In this study, PubMed, Embase, and Cochrane Database were used to search the literature from 1 January 1960 to 26 December 2022 to investigate the association between tea intake and gynecologic cancer risk. In total, 19 cohort studies with 2,020,980 subjects and 12,155 gynecological tumor cases were retrieved. The pooled relative risk (RR) of gynecologic tumor for tea intake was 1.00 (95% CI: 0.96–1.04). RRs were 0.94 (95% CI: 0.88–1.01) for ovarian cancer, 1.02 (95% CI: 0.97–1.07) for endometrial cancer, and 1.06 (95% CI: 0.91–1.23) for cervical cancer. Subgroup analyses were adopted based on the tea type and geographic location. Interestingly, significant preventive impact of non-herbal tea on ovarian cancer (pooled relative risk: 0.67; 95% CI: 0.55–0.81) was found, especially for black tea (pooled relative risk: 0.64; 95% CI: 0.51–0.80). Dose–response analysis indicated that although it is not statistically significant, a decreasing trend of ovarian cancer risk could be observed when the tea consumption was 1.40 to 3.12 cups/day. In conclusion, our findings suggested that ovarian cancer, but not other gynecologic cancers, could possibly be prevented by drinking non-herbal tea. In addition, the preventive impact of green tea on gynecologic cancer seemed to be relatively weak and needs further cohorts to validate it.

Empowering Strategies for Lifestyle Interventions, Diet Modifications, and Environmental Practices for Uterine Fibroid Prevention; Unveiling the LIFE UP Awareness

Uterine fibroids (UFs) are the most common prevalent benign tumor among women of reproductive age, disproportionately affecting women of color. This paper introduces an innovative management strategy for UFs, emphasizing the curbing of disease prevention and progression. Traditionally, medical intervention is deferred until advanced stages, necessitating invasive surgeries such as hysterectomy or myomectomy, leading to high recurrence rates and increased healthcare costs. The strategy, outlined in this review, emphasizes UF disease management and is named LIFE UP awareness—standing for Lifestyle Interventions, Food Modifications, and Environmental Practices for UF Prevention. These cost-effective, safe, and accessible measures hold the potential to prevent UFs, improve overall reproductive health, reduce the need for invasive procedures, and generate substantial cost savings for both individuals and healthcare systems. This review underscores the importance of a proactive UF management method, paving the way for future research and policy initiatives in this domain.

Metabolomic Analysis of Vitamin E Supplement Use in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases.

Vitamin D Significantly Inhibits Carcinogenesis in the Mogp-TAg Mouse Model of Fallopian Tube Ovarian Cancer

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration

Modeling of Intracellular Taurine Levels Associated with Ovarian Cancer Reveals Activation of p53, ERK, mTOR and DNA-Damage-Sensing-Dependent Cell Protection

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine’s suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine’s ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine’s cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transduction.

Blood Iodine as a Potential Marker of the Risk of Cancer in BRCA1 Carriers

Breast cancer and ovarian cancer pose a significant risk for BRCA1 carriers, with limited risk-reduction strategies. While improved screening helps in the early detection of breast cancer, preventive measures remain elusive. Emerging evidence suggests a potential link between iodine levels and modulation of cancer risk, but comprehensive studies are scarce. We conducted a prospective study among 989 BRCA1 carriers to assess the association between blood iodine levels and breast and ovarian cancer risk. Using inductively coupled plasma mass spectrometry, we measured blood iodine levels and observed a negative association with breast cancer risk, with a significantly lower risk observed in quartile 4 (iodine > 38.0 µg/L) compared with quartile 1 (iodine < 30 µg/L) (HR = 0.49; 95%CI: 0.27–0.87; p = 0.01). Conversely, a suggestive increase in ovarian cancer risk was observed at higher iodine levels (HR = 1.91; 95%CI: 0.64–5.67; p = 0.25). No significant association was found between iodine levels and overall cancer risk. Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy but require further validation and investigation of its effect on ovarian cancer risk and overall mortality. These findings highlight the need for personalized strategies to manage cancer risk in BRCA1 carriers.

Blood Lead Level as Marker of Increased Risk of Ovarian Cancer in BRCA1 Carriers

BRCA1 mutations substantially elevate the risks of breast and ovarian cancer. Various modifiers, including environmental factors, can influence cancer risk. Lead, a known carcinogen, has been associated with various cancers, but its impact on BRCA1 carriers remains unexplored. A cohort of 989 BRCA1 mutation carriers underwent genetic testing at the Pomeranian Medical University, Poland. Blood lead levels were measured using inductively coupled plasma mass spectrometry. Each subject was assigned to a category based on their tertile of blood lead. Cox regression analysis was used to assess cancer risk associations. Elevated blood lead levels (>13.6 μg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23–9.00; p = 0.02; multivariable: HR = 2.10; 95% CI: 0.73–6.01; p = 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.

Polyphenols Influence the Development of Endometrial Cancer by Modulating the Gut Microbiota

Dysbiosis of the microbiota in the gastrointestinal tract can induce the development of gynaecological tumours, particularly in postmenopausal women, by causing DNA damage and alterations in metabolite metabolism. Dysbiosis also complicates cancer treatment by influencing the body’s immune response and disrupting the sensitivity to chemotherapy drugs. Therefore, it is crucial to maintain homeostasis in the gut microbiota through the effective use of food components that affect its structure. Recent studies have shown that polyphenols, which are likely to be the most important secondary metabolites produced by plants, exhibit prebiotic properties. They affect the structure of the gut microbiota and the synthesis of metabolites. In this review, we summarise the current state of knowledge, focusing on the impact of polyphenols on the development of gynaecological tumours, particularly endometrial cancer, and emphasising that polyphenol consumption leads to beneficial modifications in the structure of the gut microbiota.

The Role of Nutrition in Pathogenesis of Uterine Fibroids

Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women’s quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.

Associations of Dietary Glycemic Index, Glycemic Load and Carbohydrate with the Risk of Cervical Intraepithelial Neoplasia and Cervical Cancer: A Case-Control Study

Background: The association of dietary glycemic index (GI) and glycemic load (GL) with the risk of cervical cancer has never been investigated. Thus, we aimed to find evidence of any association of GI and GL with the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: In this hospital-based case-control study, we included 1340 women (670 controls and 262, 187 and 221 patients with CIN1, CIN2/3, and cervical cancer, respectively) from the Korean human papillomavirus cohort study. Completed demographic questionnaires and semi-quantitative food-frequency questionnaires were collected. The association of dietary GI and GL with CIN and cervical cancer was estimated using a logistic regression model. Results: The multivariate odds ratios (OR) of the highest compared with the lowest quintile of GL for CIN1 were 2.8 (95% confidence interval (CI) = 1.33–5.88). Dietary GI and GL were not associated with CIN2/3 and cervical cancer. Stratified analyses by body mass index (BMI) indicated a positive association between GI and GL and CIN 1 risk among women with a BMI (in kg/m2) <23 (OR = 2.94; 95% CI = 1.32–6.53; p for trend = 0.031 for GI and OR = 3.15; 95% CI = 1.53–6.52; p for trend = 0.013 for GL), but not among those with a BMI of ≥23. A stratification analysis by menopausal status showed that the highest quintile of GI and GL was significantly associated with the risk of CIN1 (OR = 2.91; 95% CI = 1.43–5.96; p for trend = 0.005) (OR = 2.96; 95% CI = 1.53–5.69; p for trend = 0.023) among premenopausal women. Also, in HPV positive women, dietary GL showed significant CIN1 risk (OR = 2.61; 95% CI = 1.09–6.24; p for trend = 0.087). Conclusion: Our case-control study supports the hypothesized associations of dietary GI and GL with increased risk of CIN1. Thus, the consumption of low GI and GL foods plays a significant role in the prevention of cervical carcinogenesis.

The Effect of Vitamin D and Its Analogs in Ovarian Cancer

Ovarian cancer is one of the deadliest cancers in women, due to its heterogeneity and usually late diagnosis. The current first-line therapies of debulking surgery and intensive chemotherapy cause debilitating side effects. Therefore, there is an unmet medical need to find new and effective therapies with fewer side effects, or adjuvant therapies, which could reduce the necessary doses of chemotherapeutics. Vitamin D is one of the main regulators of serum calcium and phosphorus homeostasis, but it has also anticancer effects. It induces differentiation and apoptosis, reduces proliferation and metastatic potential of cancer cells. However, doses that would be effective against cancer cause hypercalcemia. For this reason, synthetic and less calcemic analogs have been developed and tested in terms of their anticancer effect. The anticancer role of vitamin D is best understood in colorectal, breast, and prostate cancer and much less research has been done in ovarian cancer. In this review, we thus summarize the studies on the role of vitamin D and its analogs in vitro and in vivo in ovarian cancer models.

Role of Vitamin K in Selected Malignant Neoplasms in Women

The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.

Sarcopenia as an Independent Risk Factor for Specific Cancers: A Propensity Score-Matched Asian Population-Based Cohort Study

Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.

Dietary Antioxidant Intake and Human Papillomavirus Infection: Evidence from a Cross-Sectional Study in Italy

Several lines of evidence suggested that antioxidants might play a protective role against high-risk human papillomavirus (hrHPV) infection and cervical cancer. However, the effect of combined intake of antioxidants has not been investigated thus far. The current cross-sectional study aimed to understand the relationship between dietary antioxidant intake and the risk of high-risk HPV (hrHPV) infection among 251 Italian women with normal cervical cytology. Women were tested for hrHPV using the Digene HC2 HPV DNA Test. Dietary antioxidant intakes were assessed using a semi-quantitative food frequency questionnaire, and a Composite Dietary Antioxidant Index (CDAI) was constructed on the basis of zinc, selenium, manganese, vitamin A, vitamin C, vitamin E, carotenoid, and flavonoid intake. Logistic regression analysis was used to assess odds ratio (OR) and 95% confidence interval (95% CI) for the associations of antioxidant intakes or CDAI with hrHPV status, adjusting for age, smoking status, body mass index, parity, educational level, marital status, and use of multivitamins and oral contraceptives. We first observed that hrHPV-positive women (n = 84) reported lower intake of zinc, manganese, and vitamins A and C than non-infected women. Specifically, we found a negative association between dietary intake of zinc and hrHPV-positive status when all antioxidants were considered simultaneously (OR = 0.46; 95% CI = 0.27–0.80; p = 0.006). With respect to cumulative dietary antioxidant intake, we demonstrated that women with high CDAI (third tertile) had lower odds of being hrHPV-positive than those with low CDAI (first tertile) (OR = 0.39; 95% CI = 0.18–0.85; p = 0.018). To our knowledge, this is the first study demonstrating that a diet based on the combined intake of nutrients with antioxidant properties might reduce the risk of hrHPV infection. However, further research is needed to understand whether dietary antioxidant intake is associated with hrHPV infection or its persistence.

Resveratrol against Cervical Cancer: Evidence from In Vitro and In Vivo Studies

Cervical cancer affects many women worldwide, with more than 500,000 cases diagnosed and approximately 300,000 deaths each year. Resveratrol is a natural substance of the class of phytoalexins with a basic structure of stilbenes and has recently drawn scientific attention due to its anticancer properties. The purpose of this review is to examine the effectiveness of resveratrol against cervical cancer. All available in vitro and in vivo studies on cervical cancer were critically reviewed. Many studies utilizing cervical cancer cells in culture reported a reduction in proliferation, cell cycle arrest, and induction of apoptosis. Apart from apoptosis, induction of autophagy was seen in some studies. Importantly, many studies have shown a reduction in the HPV oncoproteins E6 and E7 and increased levels of the tumor suppressor p53 with resveratrol treatment. A few studies examined the effects of resveratrol administration in mice ectopic-xenografted with cervical cancer cells showing reduced tumor volume and weight. Overall, the scientific data show that resveratrol has the ability to target/inhibit certain signaling molecules (EGFR, VEGFR, PKC, JNK, ERK, NF-kB, and STAT3) involved in cervical cancer cell proliferation and survival. Further in vivo experiments and clinical studies are required to better understand the potential of resveratrol against cervical cancer.

The Association of Dietary Diabetes Risk Reduction Score and the Risk of Cancer: A Systematic Review and Meta-Analysis of Observational Studies

Background/Objectives: Several studies have suggested a contrasting link between a diabetes risk reduction diet (DRRD) pattern and cancer risk; however, their findings have been inconsistent. This study aims to systematically review observational studies and, where possible, quantify the overall effect through a meta-analysis. Methods: Searches were conducted in PubMed, Scopus, and Web of Science through May 2025. Odds ratios (ORs), along with their confidence intervals, were extracted for meta-analysis. The random-effects model was used to combine the ORs. Results: Nineteen studies met the inclusion criteria for the systematic review and meta-analysis. Of these, six reports examined the relationship between the DRRD and breast cancer risk, three assessed liver cancer incidence, two analyzed pancreatic cancer risk, and two focused on endometrial cancer. Additionally, seven studies explored the association with other cancers, including ovarian, colorectal, renal, head and neck, bladder, and lung cancers. The meta-analysis revealed that high adherence to the DRRD is associated with a decreased cancer risk (OR = 0.77, 95% confidence interval [95% CI]: 0.71–0.84, p < 0.001). Conclusions: After stratifying by geographic region, gender, study design, and cancer site, the inverse relationship remained significant across all subgroups. DRRD can be viewed as a beneficial approach associated with a lower cancer risk.