Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium.

BACKGROUND: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. METHODS: We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. RESULTS: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. CONCLUSIONS: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. IMPACT: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Psychological factors increase the risk of ovarian cancer.

This study evaluated whether psychological stress increases the incidence of ovarian cancer. A literature search of the electronic databases PubMed and Web of Science from the date of inception to August 2022 was undertaken. Studies with data on psychosocial factors associated with ovarian cancer incidence were included in this study. A random-effect model meta-analysis was undertaken to estimate these data. We used subgroup analysis to adjust for heterogeneity. A total of 4 articles, 10 sets of data, 8 cohort studies, and 2 case-control studies from 682 records were included in this review. Meta-analyses of the included cohort study subgroups suggested that psychological factors increase the risk of ovarian cancer (effect size = 1.37, 95% CI: 1.20-1.53); the subgroup of case-control studies suggested that psychological factors did not increase ovarian cancer risk (effect size = 0.84, 95% CI: 0.70-0.98). These findings indicate that psychological stress is a possible new risk factor for ovarian cancer.Prospero registration number: CRD42022357983IMPACT STATEMENTWhat is already known on this subject? Psychological stress has been shown to increase the risk of many diseases. The relationship between psychological stress and the incidence of ovarian cancer has not been confirmed.What do the results of this study add? The effect of psychological stress on the risk of ovarian cancer was estimated using meta-analysis as an overall ratio.What are the implications of these findings for clinical practice and/or further research? Relaxing psychological stress and appropriate psychotherapy in clinical settings can help reduce the risk of ovarian cancer.

Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis.

BACKGROUND: The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence. METHODS: A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810). RESULTS: Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/- HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422-0.811) and OS (HR, 0.519; 95% CI, 0.346-0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684-1.571) or OS (HR, 0.932; 95% CI, 0.607-1.430). Consistent results were observed in subsequent sensitivity analyses. CONCLUSION: Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

Posterior pelvic exenteration for ovarian cancer: surgical and oncological outcomes.

OBJECTIVE: Posterior pelvic exenteration (PPE) can be required to achieve complete resection in ovarian cancer (OC) patients with large pelvic disease. This study aimed to analyze morbidity, complete resection rate, and survival of PPE. METHODS: Ninety patients who underwent PPE in our Comprehensive Cancer Center between January 2010 and February 2021 were retrospectively identified. To analyze practice evolution, 2 periods were determined: P1 from 2010 to 2017 and P2 from 2018 to 2021. RESULTS: A 82.2% complete resection rate after PPE was obtained, with rectal anastomosis in 96.7% of patients. Complication rate was at 30% (grade 3 in 9 patients), without significant difference according to periods or quality of resection. In a binary logistic regression adjusted on age and stoma, only age of 51-74 years old was associated with a lower rate of complication (odds ratio=0.223; p=0.026). Median overall and disease-free survivals (OS and DFS) from initial diagnosis were 75.21 and 29.84 months, respectively. A negative impact on OS and DFS was observed in case of incomplete resection, and on DFS in case of final cytoreductive surgery (FCS: after ≥6 chemotherapy cycles). Age ≥75-years had a negative impact on DFS for new OC surgery. For patients with complete resection, OS and DFS were decreased in case of interval cytoreductive surgery and FCS in comparison with primary cytoreductive surgery. CONCLUSION: PPE is an effective surgical measure to achieve complete resection for a majority of patients. High rate of colorectal anastomosis was achieved without any mortality, with acceptable morbidity and high protective stoma rate.

Hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer.

BACKGROUND: To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer. MATERIALS AND METHODS: Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed. RESULTS: Among the 51 patients, median peritoneal cancer index score was 13 (range 3-34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapy <2 lines (HR 0.24, 0.11-0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09-0.37; p < 0.001) and CA125 < 35 U/mL before HIPEC (HR 0.133, 0.021-0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion. CONCLUSIONS: The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapy <2 lines, chemotherapy-free interval ≥6 months and CA125 < 35 U/mL before HIPEC.

The effect of folate intake on ovarian cancer risk: A meta-analysis of observational studies.

BACKGROUND: Previous publications studied the correction about folate intake and ovarian cancer risk, with inconsistent results. This meta-analysis aimed to explore the association between folate intake and ovarian cancer risk using the existing published articles. METHOD: We searched for relevant studies in electronic databases of PubMed, Web of Science, Embase, Cochrane, and Wanfang databases from inception to May 31, 2020. The overall relative risk (RR) and its 95% confidence intervals (95% CI) were pooled using a random-effect model. RESULTS: A total of 12 articles with 6304 ovarian cancer cases were suitable for the inclusion criteria. The evaluated of the ovarian cancer risk with total folate intake and dietary folate intake were reported in 6 articles and 10 articles, respectively. Overall, highest category of dietary folate intake compared with lowest category had nonsignificant association on the risk of ovarian cancer (RR = 0.90, 95% CI = 0.77-1.06). The association was not significant between total folate intake and ovarian cancer risk (RR = 1.06, 95% CI = 0.89-1.27). The results in subgroup analyses by study design and geographic location were not changed either in dietary folate intake analysis or in total folate intake analysis. CONCLUSION: Our meta-analysis demonstrates that folate intake had no significant association on the risk of ovarian cancer. Study design and geographic location were not associated with ovarian cancer while some other related factors were not investigated due to the limited information provided in each included study. Therefore, further studies are needed to verify our results.

Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis.

BACKGROUND: The association between vitamin D/calcium and risk of ovarian cancer is still a debatable point. The aim of our study was to systematically investigate the association between vitamin D/calcium, and the risk of ovarian cancer and estimate their dose-response association quantitatively. METHODS: PubMed, EMBASE, and Web of Science databases were searched to identify relevant observational studies. Two investigators screened citations and extracted data independently. Data were extracted and the association between vitamin D/calcium and ovarian cancer risk was estimated by calculating pooled relative risks (RRs). Subgroup analyses, publication bias estimation, and dose-response analyses were carried out as well. RESULTS: In total, 21 articles involving 980,008 participants were included in our present study. No significant association was observed between total vitamin D intake and ovarian cancer risk (RR: 1.02; 95% CI, 0.89-1.16, p = 0.81). Further subgroup analysis suggested that neither dietary vitamin D intake (RR: 0.80; 95% CI, 0.62-1.03, p = 0.09) nor supplementary vitamin D intake (RR: 0.98; 95% CI, 0.85-1.13, p = 0.80) was associated with the risk of ovarian cancer. As for calcium, total calcium intake was found to be statistically inversely associated with ovarian cancer risk in case-control studies (RR: 0.73; 95% CI, 0.63-0.86, p < 0.001) but not in cohort studies (RR: 1.05; 95% CI, 0.90-1.24, p = 0.52). Besides, supplementation with calcium plus vitamin D was not effective for the prevention of ovarian cancer (p = 0.98). Of note, dose-response analysis based on cohort studies suggested a potential inverse U-shape relationship between calcium intake (including total calcium and dietary calcium) and ovarian cancer risk, which indicated that low dose of calcium intake might reduce ovarian cancer risk while high dose of calcium intake might not. CONCLUSIONS: Taken together, vitamin D could not decrease the risk of ovarian cancer. The role of calcium intake was not proven for reducing ovarian cancer risk. Besides, no evidence showed combinative use of calcium and vitamin D have additional benefits for ovarian cancer prevention.

Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer.

One of the major challenges in the treatment of cancer are differential responses of patients to existing standard of care anti-cancer drugs. These differential responses may, in part, be due to a diverse range of genomic, epigenomic, proteomic, and metabolic alterations among individuals suffering from the same type of cancer. Precision medicine is an emerging approach in cancer therapeutics that takes into account specific molecular alterations, environmental factors as well as lifestyle of individual patients. This approach allows clinicians and researchers to select or predict treatments that would most likely benefit the patient based on their individual tumor characteristics. One class of precision medicine tools are predictive, in vitro drug-response assays designed to test the sensitivity of patient tumor cells to existing or novel therapies. These assays have the potential to rapidly identify the most effective treatments for cancer patients and thus hold great promise in the field of precision medicine. In this review, we have highlighted several drug-response assays developed in ovarian cancer and discussed the current challenges and future prospects of these assays in the clinical management of this disease.

High RIG-I expression in ovarian cancer associates with an immune-escape signature and poor clinical outcome.

Ovarian cancer (OC) is the most lethal gynecological malignancy, with platinum-based chemotherapy remaining the mainstay for adjuvant treatment after surgery. The lack of indication for immunotherapy may at least in part result from the lack of suitable biomarkers allowing stratification of potentially responding patients. In this monocentric study of 141 cases with OC, we used real-time quantitative PCR to assess the expression of retinoic acid-inducible gene-I (RIG-I) in primary tumor and healthy ovarian control tissues. RIG-I expression was correlated to various clinicopathological characteristics as well as to a set of molecular and immunological markers. The prognostic significance of RIG-I expression was queried in univariate and multivariate analyses and validated in an independent cohort. RIG-I was overexpressed in the cancerous ovary and correlated with a higher tumor grade. The more aggressive Type-II cancers and cancers with inactivating p53 mutations exhibited higher RIG-I expression. RIG-I levels were also elevated in cancers that recurred after remission or were platinum-refractory. Survival analyses disclosed RIG-I as an independent marker of poor outcome in OC. Continuative analyses revealed the molecular and immunological correlates of RIG-I expression in the tumor microenvironment, including interferon production and a distinct immune-regulatory signature involving checkpoint molecules (PD-L1/PD-1), the RNA-editing enzyme ADAR1 and the regulatory T cell-specific transcription factor FoxP3. We conclude that high RIG-I expression associates with poor outcome in OC, which is explainable by local immunosuppression in the tumor bed. RIG-I expression may inform checkpoint blockade and/or RIG-I agonistic targeting in a subset of high-risk OC patients.

[Influence of food or food groups intake on the occurrence and/or protection of different types of cancer: systematic review]. / Influencia de la ingesta de alimentos o grupos de alimentos en la aparición y/o protección de los diversos tipos de cáncer: revisión sistemática.

INTRODUCTION: Introduction: the diet plays an important role in the origin and prevention of multiple chronic degenerative diseases, such as cardiovascular diseases or cancer. Objective: the main objective of this paper is to analyze the studies that are focused on researching the relationship between the consumption of the particular groups of foods and its importance on the increase and for prevention of the risk of cancer appearance. Methods: a bibliographical review was carried out in the main international databases (PubMed, Scopus and Nutrition Reference). The results were structured in two main sections: those related with the increase of cancer risk and food related with the increase of cancer risk. In the present review, 104 scientific articles have been evaluated. Results: the results have shown a positive association between red meat and colon cancer, alcoholic drinks and liver cancer, and salt and gastric cancer. The Mediterranean diet was associated in a preventive way with digestive and respiratory tract cancer. Conversely, no statistically significant association was found between dairy products and ovarian cancer, carbohydrates and sugars and pancreatic cancer, and tae and breast cancer. Conclusions: as a result, healthy eating guidelines, such as the Mediterranean diet, based on lower consumption of red meat, alcoholic drinks and salt, might contribute to reducing the incidence of colon cancer, liver cancer and gastric cancer.

INTRODUCCIÓN: Introducción: la dieta tiene un importante papel en la formación y en la prevención de múltiples enfermedades crónicas-degenerativas, como son las enfermedades cardiovasculares o el cáncer. Objetivos: el objetivo principal consiste en analizar los estudios que centren su investigación en conocer la relación entre el consumo de determinados grupos de alimentos y su función en el aumento y/o prevención del riesgo de aparición de diversos tipos de cáncer. Métodos: se realizó una revisión sistemática en bases de datos internacionales (PubMed, Scopus y Nutrition Reference). Los estudios fueron estructurados en dos bloques principales: relacionados con el aumento del riesgo de cáncer y alimentos relacionados con el aumento del riesgo de cáncer. Los estudios evaluados en la presente revisión han sido un total de 104 artículos científicos. Resultados: los resultados han mostrado una asociación positiva entre la carne roja y el cáncer de colon, las bebidas alcohólicas y el cáncer de hígado y la sal y el cáncer gástrico. La dieta mediterránea se asoció de manera preventiva con el cáncer del tracto digestivo y respiratorio, mientras que, por otro lado, no se ha encontrado asociación estadísticamente significativa entre el consumo de lácteos y el cáncer de ovario, los carbohidratos o azúcares y el cáncer de páncreas y el té y el cáncer de mama. Conclusiones: por todo ello, patrones de alimentación saludable como la dieta mediterránea, basados en una menor ingesta de carne roja, bebidas alcohólicas y sal, contribuyen a una reducción en la incidencia del cáncer de colon, cáncer de hígado y cáncer de estómago.

P-MAPA and Interleukin-12 Reduce Cell Migration/Invasion and Attenuate the Toll-Like Receptor-Mediated Inflammatory Response in Ovarian Cancer SKOV-3 Cells: A Preliminary Study.

Immunotherapies have emerged as promising complementary treatments for ovarian cancer (OC), but its effective and direct role on OC cells is unclear. This study examined the combinatory effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) on cell migration/invasion, apoptosis, toll-like receptor (TLR)-mediated inflammation, and cytokine/chemokine profile in human OC cell line SKOV-3. P-MAPA and IL-12 showed cancer cell toxicity under low doses after 48 h. Although apoptosis/necrosis and the cell cycle were unchanged by the treatments, P-MAPA enhanced the sensitivity to paclitaxel (PTX) and P-MAPA associated with IL-12 significantly reduced the migratory potential and invasion capacity of SKOV-3 cells. P-MAPA therapy reduced TLR2 immunostaining and the myeloid differentiation factor 88 (MyD88), but not the TLR4 levels. Moreover, the combination of P-MAPA with IL-12 attenuated the levels of MyD88, interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB p65). The IL-12 levels were increased and P-MAPA stimulated the secretion of cytokines IL-3, IL-9, IL-10, and chemokines MDC/CCL22 and, regulated on activation, normal T cells expressed and secreted (RANTES)/CCL5. Conversely, combination therapy reduced the levels of IL-3, IL-9, IL-10, MDC/CCL22, and RANTES/CCL5. Collectively, P-MAPA and IL-12 reduce cell dynamics and effectively target the TLR-related downstream molecules, eliciting a protective effect against chemoresistance. P-MAPA also stimulates the secretion of anti-inflammatory molecules, possibly having an immune response in the OC microenvironment.

Hysterectomy and unilateral salpingectomy associate with a higher risk of subsequent ovarian cancer: A population-based cohort study in Taiwan.

Studies on the relationship between gynecologic surgery and subsequent ovarian cancer have been carried out in limited Western ethnic groups. We aim to evaluate whether receiving hysterectomy and/or salpingectomy associated with ovarian cancer risk in Taiwan.From the Taiwan National Health Insurance Research Database, we identified a gynecologic surgery cohort consisting of women who had newly received hysterectomy (N = 181,151), salpingectomy (N = 45,410) or both hysterectomy and salpingectomy (N = 11,875) in 2000 to 2013. A comparison cohort of 953,744 women was randomly selected from women without the surgeries, frequency-matched by age and index date of the surgery case. They were followed up to identify subsequent ovarian cancer by the end of 2013.The overall ovarian cancer incidence was 4.4-fold greater in the gynecologic surgery cohort than in the comparison cohort (41.5 vs 9.43 per 10 person-years) with an adjusted hazard ratio of 3.86 (95% confidence interval = 2.56-5.84). Women with both hysterectomy and salpingectomy had the highest incidence and followed by women with hysterectomy or salpingectomy (52.5, 45.5, or 23.3 per 10 person-years, respectively). No ovarian cancer was noted in the subgroup with bilateral salpingectomies.We conclude that women with gynecologic surgery of hysterectomy and/or salpingectomy are at an increased risk of developing ovarian cancer, particularly among women who have had other gynecologic comorbidity. Women with gynecologic surgery and comorbidity deserve greater attention to prevent and screen for ovarian cancer.

Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study.

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Therapeutic Targeting of Collective Invasion in Ovarian Cancer.

Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed "leader cells". Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.

Associations of coffee, tea and caffeine intake with risk of breast, endometrial and ovarian cancer among Canadian women.

BACKGROUND: Although, biologically plausible evidence has implicated coffee, tea and caffeine with carcinogenesis, there is a paucity of data on their associations with risk of cancer among Canadian women. Hence, we assessed their associations with risk of breast, endometrial and ovarian cancers within this population. METHODS: The study comprised a subcohort of 3185 women from a cohort of 39,532 female participants who completed self-administered lifestyle and dietary questionnaires at enrollment. During a median follow-up of approximately 12.2years, we ascertained 922, 180 and 104 breast, endometrial and ovarian cancer cases, respectively. We used Cox proportional hazards regression models modified for the case-cohort design to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the associations of coffee, tea and caffeine with risk of selected cancers. RESULTS: Coffee, tea, and caffeine intake were not associated with overall risk of breast and ovarian cancers. There was, however, a tendency towards an increased risk of breast cancer with increasing levels of total coffee, caffeinated coffee and/or caffeine among premenopausal and normal weight women. Total coffee, caffeinated coffee, and caffeine were inversely associated with risk of endometrial cancer (HRper cup increase: 0.88; 95% CI: 0.79-0.95, HRper cup increase: 0.88; 95% CI: 0.80-0.96 and HRper 100mg increase: 0.93; 95% CI: 0.87-0.99, respectively). CONCLUSION: Our findings suggest that coffee and/or caffeine may be associated with reduced risk of endometrial cancer but, probably, associated increased with risk of breast cancer among premenopausal or normal weight women. However, further studies are needed to confirm our findings.

Risk factors in progression from endometriosis to ovarian cancer: a cohort study based on medical insurance data.

OBJECTIVE: The objective was to identify risk factors that were associated with the progression from endometriosis to ovarian cancer based on medical insurance data. METHODS: The study was performed on a dataset obtained from the National Health Insurance Research Database, which covered all the inpatient claim data from 2000 to 2013 in Taiwan. The International Classification of Diseases (ICD) code 617 was used to screen the dataset for the patients who were admitted to hospital due to endometriosis. They were then tracked for subsequent diagnosis of ovarian cancer, and available biological, socioeconomic and clinical information was also collected. Univariate and multivariate analyses were then performed based on the Cox regression model to identify risk factors. C-index was calculated and cross validated. RESULTS: A total of 229,617 patients who were admitted to hospital due to endometriosis from 2000 to 2013 were included in the study, out of whom 1,473 developed ovarian cancer by the end of 2013. A variety of factors, including age, residence, hospital stratification, premium range, and various comorbidities had significant impact on the progression (p<0.05). Among them, age, urbanization of residence, hospital stratification, premium range, post-endometriosis childbearing, pelvic inflammation, and depression all had independent, significant impact (p<0.05). The validated C-index was 0.69. CONCLUSION: For a woman diagnosed with endometriosis, increased age, residing in a highly urbanized area, low or high income, depression, pelvic inflammation, and absence of childbearing post-endometriosis all put her at high-risk to develop ovarian cancer. The findings may be of help to gynecologists to identify high-risk patients.

Tea consumption and the risk of ovarian cancer: A meta-analysis of epidemiological studies.

A large number of epidemiological studies have provided conflicting results about the relationship between tea consumption and ovarian cancer. This study aimed to clarify the association between tea consumption and ovarian cancer. A literature search of the MEDICINE, Scopus, PubMed, and Web of Science databases was performed in April 2016. A total of 18 (11 case-control and 7 cohort) studies, representing data for 701,857 female subjects including 8,683 ovarian cancer cases, were included in the meta-analysis. A random-effects meta-analysis was used to compute the pooled relative risks (RR), meta regression, and publication bias, and heterogeneity analyses were performed for the included trials. We found that tea consumption had a significant protective effect against ovarian cancer (relative risk [RR] = 0.86; 95% confidence interval [CI]: 0.76, 0.96). The relationship was confirmed particularly after adjusting for family history of cancer (RR = 0.85; 95% CI: 0.72, 0.97), menopause status (RR = 0.85; 95% CI: 0.72, 0.98), education (RR = 0.82; 95% CI: 0.68, 0.96), BMI (RR = 0.85; 95% CI: 0.70, 1.00) , smoking (RR = 0.83; 95% CI: 0.72, 0.93) and Jadad score of 3 (RR = 0.76; 95% CI: 0.56, 0.95) and 5 (RR = 0.74; 95% CI: 0.59, 0.89). The Begg's and Egger's tests (all P > 0.01) showed no evidence of publication bias. In conclusion, our meta-analysis showed an inverse association between tea consumption and ovarian cancer risk. High quality cohort-clinical trials should be conducted on different tea types and their relationship with ovarian cancer.

Tea, coffee, and caffeinated beverage consumption and risk of epithelial ovarian cancers.

BACKGROUND: The risk for epithelial ovarian cancer associated with the consumption of caffeinated beverages (tea, coffee, and soft drinks) and green tea is inconclusive. However, few studies have investigated the type of caffeinated beverage or the type of tea. OBJECTIVE: We assessed consumption of tea (black/caffeinated tea and green tea separately), coffee, and caffeinated soft drinks, as well as level of consumption, and the risk for epithelial ovarian cancer and its histotypes. STUDY DESIGN: This study was conducted within a population-based case-control study in Alberta and British Columbia, Canada from 2001 to 2012. After restricting to cases of epithelial invasive cancers and controls aged 40-79 years who completed an interview that included coffee, soft drink, and tea consumption (ascertained starting in 2005 in British Columbia and 2008 in Alberta), there were a total of 524 cases and 1587 controls. Those that did not meet the threshold for beverage consumption (at least once per month for 6 months or more) were classified as non-drinkers. Adult lifetime cumulative consumption (cup-years=cups/day*years) was calculated. Unconditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to describe the association between the relevant drink consumption and risk. RESULTS: No excess risk was seen for coffee or caffeinated soft drinks. Similarly, any tea consumption was not associated with risk, but when stratified by the type of tea, there was an increase in risk in black tea only drinkers (aOR=1.56; 95% CI:1.07-2.28 for >40 cup-years), but no excess risk for the exclusive green tea drinkers. Similar findings were observed for post-menopausal women. The association for black tea only consumption was mainly seen in the endometrioid histotype (aOR=3.19; 95% CI: 1.32-7.69). CONCLUSION: Black tea consumption may be associated with an increased risk epithelial ovarian carcinoma. The excess risk is seen only in the endometrioid histotype but not in serous or clear cell. Further studies are required to confirm these findings and identify the constituents in black tea that may increase the risk.

[Lactose intolerance: past and present. Part II]. / A laktózintoleranciáról: Múlt és jelen - II. rész.

The author summarises the interrelations between lactose intolerance, calcium and vitamin D metabolism and osteoporosis. Lactose intolerance enhances the risk of forearm and hip fractures in some patients. Lactase gene genotype and fracture risk are related in some populations. Calcium and vitamin D supplementation increase bone mineral content and they are justified in children, during pregnancy and lactation, and in postmenopausal women. The intake of milk and milk products could increase the risk of ovarian carcinoma. CC genotype of the lactase gene increased the risk of colorectal carcinoma in Finns; no such effect was observed in British, Spanish and Italian patients. Even small quantities of lactose in drugs (10-750 mg) could elicit intolerance symptoms due to individual susceptibility. In spite of public knowledge and advertising, controlled studies did not prove the beneficial effect of either a lactose-free diet, enzyme supplementation or probiotics in an evidence-based manner. While accepted guidelines are lacking, a personalised therapy is mandatory. In spite of increasing public interest in lactose intolerance, many unknown factors must still be studied.

Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort.

BACKGROUND: The association between coffee intake, tea intake and cancer has been extensively studied, but associations are not established for many cancers. Previous studies are not consistent on whether caffeine may be the source of possible associations between coffee and cancer risk. METHODS: In the Prostate, Lung, Colorectal, and Ovarian cancer screening trial, of the 97,334 eligible individuals, 10,399 developed cancer. Cancers included were 145 head and neck, 99 oesophageal, 136 stomach, 1137 lung, 1703 breast, 257 endometrial, 162 ovarian, 3037 prostate, 318 kidney, 398 bladder, 103 gliomas, and 106 thyroid. RESULTS: Mean coffee intake was higher in lower education groups, among current smokers, among heavier and longer duration smokers, and among heavier alcohol drinkers. Coffee intake was not associated with the risk of all cancers combined (RR=1.00, 95% confidence interval (CI)=0.96-1.05), whereas tea drinking was associated with a decreased risk of cancer overall (RR=0.95, 95% CI=0.94-0.96 for 1+ cups per day vs <1 cup per day). For endometrial cancer, a decreased risk was observed for coffee intake (RR=0.69, 95% CI=0,52-0.91 for ⩾2 cups per day). Caffeine intake was not associated with cancer risk in a dose-response manner. CONCLUSIONS: We observed a decreased risk of endometrial cancer for coffee intake, and a decreased risk of cancer overall with tea intake.