Reduction In Risk Of Endometrial Cancer Research Articles

The causal effects of genetically predicted alcohol consumption on endometrial cancer risk from a Mendelian randomization study

Endometrial cancer (EC) is a common gynecological tumor in females with an increasing incidence over the past few decades. Alcohol consumption has been linked to the occurrence of various cancers; However, epidemiological studies have shown inconsistent associations between alcohol consumption and EC risk. In order to avoid the influence of potential confounding factors and reverse causality in traditional epidemiological studies, we used a method based on genetic principles-Mendelian randomization (MR) analysis to test whether there is a causal relationship between alcohol consumption and EC. MR analysis was conducted using publicly available summary-level data from genome-wide association studies (GWAS). Fifty-seven single nucleotide polymorphisms (SNPs) were extracted as instrumental variables for alcohol exposure from the GWAS and Sequencing Consortium of Alcohol and Nicotine GWAS summary data involving 941,287 participants of European ancestry. SNPs for EC were obtained from the Endometrial Cancer Association Consortium, the Endometrial Cancer Epidemiology Consortium, and the UK Biobank, involving 121,885 European participants. The inverse variance weighted (IVW) method was used as the primary method to estimate the causal effect, and the MR-Egger regression and weighted median method were used as supplementary methods. Sensitivity analyses were conducted using the Mendelian Randomization Pleiotropy RESidual Sum and Outlier global test, MR-Egger intercept test, and leave-one-out analysis to evaluate the impact of pleiotropy on causal estimates. An increase of 1 standard deviation of genetically predicted log-transformed alcoholic drinks per day was associated with a 43% reduction in EC risk [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.41–0.79, P < 0.001]. Subgroup analysis of EC revealed that alcohol consumption was a protective factor for endometrioid endometrial cancer (EEC) (OR = 0.56, 95% CI 0.38–0.83, P = 0.004) but not for non-endometrioid endometrial cancer (NEC) (OR = 1.36, 95% CI 0.40–4.66, P = 0.626). The MR-Egger regression and weighted median method yielded consistent causal effects with the IVW method. The consistent results of sensitivity analyses indicated the reliability of our causal estimates. Additionally, alcohol consumption was associated with decreased human chorionic gonadotropin (HCG) and insulin-like growth factor 1 (IGF1) levels. This MR study suggests that genetically predicted alcohol consumption is a protective factor for EC, particularly for EEC, and this protective effect may be mediated through the reduction of HCG and IGF1.

Quantifying the Effect of Physical Activity on Endometrial Cancer Risk.

Effective, low-cost primary prevention strategies are urgently needed to tackle the rapid global increase in endometrial cancer. We sought to quantify the effect of physical activity on endometrial cancer risk, noting a linear inverse relationship influenced by body mass index. The most beneficial type and amount of activity remain unclear.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Coffee Decreases the Risk of Endometrial Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Aim: The aim of this study was to perform a comprehensive meta-analysis of the association between coffee consumption and risk of endometrial cancer. Methods: Eligible studies were identified by searching the PubMed and EMBASE databases. The dose–response relationship as well as the risk of endometrial cancer for the highest versus the lowest categories of coffee consumption were assessed. Subgroup analyses considering the menopausal and receptor statuses, the smoking status, and the BMI (Body Mass Index) were performed in order to identify potential confounders. Results: We identified a total of 12 studies eligible for meta-analysis. A dose–response meta-analysis showed a decreased risk of endometrial cancer. Moreover, a subgroup analysis indicated that coffee consumption is significantly associated with a decreased risk of postmenopausal cancer. Increasing coffee consumption by four cups per day was associated with a 20% reduction in endometrial cancer risk (relative risk (RR) 0.80; 95% confidence interval (CI) 0.72 to 0.89) and with a 24% reduction in postmenopausal cancer risk (RR 0.76; 95% CI 0.69 to 0.83). Conclusions: Our findings suggest that increased coffee consumption is associated with decreased risk of endometrial cancer, and this association is observed also for postmenopausal cancer.

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis.

Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

Circulating adiponectin and risk of endometrial cancer.

BackgroundAdiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer.MethodsPubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies.ResultsA total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found.ConclusionsThis meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer.

Oral bisphosphonate use and risk of postmenopausal endometrial cancer.

Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry. During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use. In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.

Abstract 1268: High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the norwegian women and cancer study: A population-based prospective study

Abstract Background Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. Methods A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. Results During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. Conclusions These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method. Citation Format: Oxana Gavrilyuk, Tonje Braaten, Guri Skeie, Elisabete Weiderpass, Vanessa Dumeaux, Eiliv Lund. High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the norwegian women and cancer study: A population-based prospective study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1268. doi:10.1158/1538-7445.AM2014-1268

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian Women and Cancer Study: a population-based prospective study

BackgroundCoffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country.MethodsA total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods.ResultsDuring an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers.ConclusionsThese data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

Hormone Contraception before the First Birth and Endometrial Cancer Risk

There is a well-documented reduction in endometrial cancer risk with combined oral contraceptive (COC) use. COC use before the first full-term pregnancy may affect breast cancer risk for decades, but this relationship has not been investigated in endometrial cancer. We investigated the risk for endometrial cancer with COC use before the first full-term pregnancy. Cases (n = 524) from a population-based cancer registry and age-matched controls (n = 1,032) were recruited between 2002 and 2006 in Alberta, Canada. Participants completed an in-person interview and provided detailed information on exogenous hormone use and other risk factors. Risk reductions in endometrial cancer with COC use over the premenopausal years were consistent with the published literature. We also found evidence of a long-term, significant risk reduction in parous women with COC use before the first full-term pregnancy. Among parous women, ≥5 years of COC use before a first full-term pregnancy was associated with a significant reduction in risk [adjusted OR, 0.42; 95% confidence interval (CI), 0.25-0.72], even if this exposure was a woman's only use of COCs (adjusted OR, 0.35; 95% CI, 0.18-0.68). Further understanding of the long-term effects of COC use may help guide the timing of chemoprevention efforts via COCs.

Hormonal and Reproductive Risk Factors for Sporadic Microsatellite Stable and Unstable Endometrial Tumors

Hormonal and reproductive factors modulate bioavailable estrogen to influence endometrial cancer risk. Estrogen affects the microsatellite status of tumors, but the relation between these estrogen-related factors and microsatellite instability (MSI) status of endometrial tumors is not known. We evaluated associations between hormonal and reproductive factors and risks of microsatellite stable (MSS) and MSI endometrial cancer among postmenopausal women (MSS cases = 258, MSI cases = 103, and controls = 742) in a population-based case-control study in Alberta, Canada (2002-2006). Polytomous logistic regression was used to estimate ORs and 95% confidence intervals (95% CI). We observed a significant trend in risk reduction for MSI (Ptrend = 0.005) but not MSS (Ptrend = 0.23) cancer with oral contraceptive use; with 5-year use or more, the risk reduction was stronger for MSI (OR = 0.42; 95% CI, 0.23-0.77) than for MSS cancer (OR = 0.80; 95% CI, 0.54-1.17; Pheterogeneity = 0.05). For more recent use (<30 years), the risk reduction was stronger for MSI (OR = 0.36; 95% CI, 0.19-0.69) than for MSS cancer (OR = 0.77; 95% CI, 0.51-1.15; Pheterogeneity = 0.032). No differential risk associations were observed for menopausal hormone use, parity and age at menarche, menopause or first pregnancy. We found limited evidence for statistical heterogeneity of associations of endometrial cancer risk with hormonal and reproductive factors by MSI status, except with oral contraceptive use. This finding suggests a potential role for the MMR system in the reduction of endometrial cancer risk associated with oral contraceptive use, although the exact mechanism is unclear. This study shows for the first time that oral contraceptive use is associated with a reduced risk for MSI but not for MSS endometrial cancer.

Re: A prospective investigation of coffee drinking and endometrial cancer incidence

authors show statistically significant inverse associations for both caffeinated coffee and decaffeinated coffee, with per-cup hazard ratios of 0.90 (0.86–0.95) and 0.93 (0.87–0.99), respectively, and conclude that the observed reduction in endometrial cancer risk does not differ by caffeine content. In this letter, we attempt to provide an alternate interpretation for the results from this study, especially with regard to caffeinated and decaffeinated coffee. The examination of Table 2 in Ref. 1 reveals a greater magnitude of reduction in endometrial cancer risk with caffeinated coffee than with decaffeinated coffee. Compared to nondrinkers, hazard ratios for caffeinated coffee drinkers are 0.68 (0.53–0.87) and 0.46 (0.34–0.63) for 1 cup and >3 cups per day, respectively. Hazard ratios for decaffeinated coffee drinkers are 0.81 (0.62–1.06) and 0.81 (0.51–1.20) for 1 cup and >3 cups per day, respectively. Even though the p-trend is statistically significant for both coffee types, the 95% confidence intervals are consistently significant only for caffeinated coffee. Proposed biological mechanisms would predict a stronger association for caffeinated coffee than for decaffeinated coffee. Caffeinated coffee/caffeine is associated with higher levels of adiponectin levels, 5 an endogenous insulin sensitizer, and higher levels of sex hormone binding globulin (SHBG), a moiety that reduces bioavailable estrogen. 6,7 If coffee consumption influences endometrial cancer risk by reducing bioavailable estrogen and insulin levels, then there is greater plausibility for caffeinated coffee than for decaffeinated coffee. These mechanistic associations have not been observed for decaffeinated coffee. 5,7 Interestingly, in line with an insulin-mediated mechanism, a recent study suggested that coffee may reduce diabetes risk through SHBG, an association that is apparent for caffeinated coffee and caffeine, but not for decaffeinated coffee. 7 Both types of coffee are associated with lower C-peptide levels 8 and contain other compounds that may reduce endometrial cancer risk such as cholorogenic acid and antioxidants. Although it is possible that both types of coffee may reduce endometrial cancer risk, caffeine would be predicted to provide added reduction in risk. The method of exposure assessment used to ascertain caffeinated or decaffeinated coffee drinkers further provides room for misclassification across coffee types. Participants were asked to report the number of cups of coffee they drank. They were then asked to indicate whether they drank caffeinated or decaffeinated coffee more than half the time. Using only this information, those who drank decaffeinated coffee more than 50% of the time could, by definition, have also consumed some amount of caffeinated coffee. We can hypothesize that the reduction in risk in decaffeinated coffee could in part be due to caffeinated coffee or visa versa. However, given the strength of the proposed underlying biologic rationale for caffeinated coffee, the greater magnitude in reduction observed for caffeinated coffee than for decaffeinated coffee, and the inherent misclassification due to the way coffee type was determined, it is more likely that some of the reduction observed in decaffeinated coffee drinkers could in fact be attributed to caffeine. It is also of note that decaffeinated coffee contains small amounts of caffeine and that this study did not assess information on other sources of caffeine such as tea, soda and chocolate.

Oral contraception and risk of endometrial cancer

Oral contraception and risk of endometrial cancer Alfred O Mueck1, Harald Seeger1, Xiangyan Ruan2 1Department of Endocrinology and Menopause, University Women&#39;s Hospital of Tuebingen, Tuebingen, Germany; 2Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China Abstract: No placebo-controlled studies concerning hormonal contraception in general have been published, and only investigations on biological mechanisms and observational clinical studies are available. Thus, associations can be described but not their causality. Experimental studies strongly suggest protective effects of the progestagen component of hormonal contraception against development of estrogen-related (type 1) endometrial cancer. In light of this research, it seems biologically plausible that, in more than 20 published studies, a reduction in endometrial cancer risk was achieved in up to 50% of users of combined oral contraceptives (COC), compared with nonusers. Few data exist for progestin-only oral preparations. However, in view of the mechanisms involved, a reduction in cancer risk should also be expected. Whereas hormonal dose-dependency has been investigated in only a few studies, which showed a stronger risk reduction with increasing progestagenic potency, a decreased risk dependent on duration of use has been clearly demonstrated, and after stopping COC this effect has persisted for up to 20 years. Possible confounders, including family history, parity, and smoking, have been investigated in a few studies, with only a minor impact on hormonal effect of endometrial cancer risk, with the exception of obesity, which was a strong risk factor in most but not all studies. There are obvious differences in the incidence of endometrial cancer in women using COC when evaluated in absolute numbers for Western and Asian countries, being about 3&ndash;5-fold higher in the US than in Asia. Further research should include the noncontraceptive benefit of COC, especially in patients with a high risk of cancer, as in polycystic ovary disease, and should also include new contraceptive drugs using natural estradiol instead of ethinyl estradiol. Of importance is the question of the potency of hormonal intrauterine devices to protect against endometrial cancer. It can be concluded on the basis of biological plausibility and observational data that COC can strongly decrease the risk of estrogen-related endometrial cancer, with an effect persisting after withdrawal of the hormones, and a causal relationship for this protection against cancer seems reasonable. Keywords: hormonal contraceptives, endometrial cancer

Abstract 1900: Age at last birth and endometrial cancer risk: Pooled analysis in the Epidemiology of Endometrial Cancer Consortium

Abstract Some studies show that childbearing at older age is associated with lower risk of endometrial cancer, but whether the association is independent of number of children or other factors still requires clarification. We pooled individual-level data from epidemiologic studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Data on age at last birth and/or last pregnancy were available from 14 studies: 11 case-control studies and 3 cohort studies; the latter were analyzed using a nested case-control design. A total of 9,613 endometrial cancer cases and 17,112 controls were included in the analysis. The majority of women were White (82%) and older than 55 years (69%). We estimated the effects of age at last birth using data from 12 studies and age at last pregnancy using data from 10 studies on the risk of endometrial cancer by calculating odds ratios (OR) and 95% confidence intervals (95% CI) using logistic regression models. Potential confounders included in the analysis were race, body mass index, parity, age at menarche, age at first birth, oral contraceptive use, postmenopausal hormone use, smoking status, and report of diabetes. After adjusting for potential confounders, a reduction in endometrial cancer risk was observed in women with increasing age at last birth (P trend &amp;lt;0.0001) and age at last pregnancy (P trend &amp;lt;0.0001). The OR per five-year increase in age at last birth and age at last pregnancy was 0.90 (95%CI: 0.86, 0.94) and 0.91 (95% CI: 0.87, 0.95), respectively. Women who had their last child at an age &amp;gt;40 years were at a 34% decreased risk compared with women who had their last child at an age &amp;lt;25 years (95% CI: 0.52, 0.82). Compared to women with age at last pregnancy &amp;lt;25 years, those with age at last pregnancy &amp;gt;40 years had a 30% decreased risk of endometrial cancer (95%CI: 0.57, 0.86). Inverse associations were observed for Whites and Asians in race-specific analysis and also in analysis restricted to women with at least 2 births. In this large pooled analysis, we show that late age at last birth or last pregnancy is a strong and independent protective factor for endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1900. doi:10.1158/1538-7445.AM2011-1900

Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.

Phytoestrogen consumption and endometrial cancer risk: a population-based case–control study in New Jersey

Phytoestrogens have been shown to exert anti-estrogenic and estrogenic effects in some tissues, including the breast. However, only a few studies have evaluated their role in endometrial cancer risk. We evaluated this association in a population-based case-control study in New Jersey. A total of 424 cases and 398 controls completed an interview, including a food frequency questionnaire with supplemental questions for phytoestrogen foods. Risk estimates were derived using an unconditional logistic regression, adjusting for major risk factors for endometrial cancer. There was some suggestion of a decreased risk with quercetin intake (OR: 0.65; 95% CI: 0.41-1.01 for the highest compared to the lowest quartile; p for trend: 0.02). We found a limited evidence of an association with any of the lignans evaluated, total lignans, coumestrol, individual isoflavones, total isoflavones, or total phytoestrogens. However, there was some suggestion of an inverse association with total isoflavone intake limited to lean women (BMI <25; OR for the highest tertile: 0.50; 95% CI: 0.25-0.98) and those with a waist-to-hip ratio <or=0.85 (OR: 0.59; 95% CI: 0.33-1.05). There was no evidence of effect modification by HRT use. This study suggests a reduction in endometrial cancer risk with quercetin intake and with isoflavone intake in lean women.

Statin use and female reproductive organ cancer risk in a large population-based setting.

Statins are an effective and commonly used cholesterol-lowering medication class, but their hypothesized effects on cancer risk remain uncertain. We evaluated the association between statin use and endometrial as well as ovarian cancer risks. We conducted a retrospective study with two cohorts of women aged 45-89 years during 1990-2004 within an integrated healthcare delivery system. Information on statin use and covariates were obtained from automated databases. We identified cancer cases through the Surveillance, Epidemiology, and End Results registry. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for incident invasive endometrial and ovarian cancers among statin users compared to nonusers. Women were followed for a median of about six years. Among 73,336 women studied, 568 endometrial cancer cases were identified. During the study period, 6% of women used statins for at least one year and the median duration of use was 3.1 years. Although not statistically significant, we found a reduction in endometrial cancer risk among statin users (HR = 0.67; 95% CI: 0.39-1.17) compared to nonusers. We identified 326 ovarian cancer cases in a cohort of 93,619 women. There was also a nonsignificant decrease in ovarian cancer risk among statin users (HR = 0.69; 95% CI: 0.32-1.49). Our study does not support an association between statin use and endometrial as well as ovarian cancers, but a reduced risk cannot be ruled out.

Risk of endometrial cancer in relationship to cigarette smoking: Results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.

Dietary Folate Intake,MTHFRGenetic Polymorphisms, and the Risk of Endometrial Cancer among Chinese Women

Folate plays an important role in carcinogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene, is involved in this process. We investigated both the independent and joint effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk in a population-based case-control study. Between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls were recruited among women between the ages of 30 and 69 years in urban Shanghai, China. Information on dietary intake of folate and other methyl-related nutrients, including vitamin B2 (riboflavin), vitamin B6, vitamin B12, and methionine, was derived from a validated food frequency questionnaire. Genotyping was completed on 1,041 cases and 1,030 controls for MTHFR 677C>T (rs1801133), 1298A>C (rs1801131), and 1793 G>A (rs2274967) [corrected] Haplotype estimation of the three single-nucleotide polymorphisms was performed using PHASE software. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate associations of nutrients, MTHFR genotypes, and haplotypes with endometrial cancer risk. A significant inverse association between dietary folate intake and endometrial cancer risk was observed among all subjects and non-B vitamin supplement users. The greatest reduction in endometrial cancer risk was observed among non-users of supplements in the highest quartile of dietary folate intake (OR, 0.5; 95% CI, 0.4-0.7) as compared with those in the lowest quartile. Dietary intake of folate cofactors (methionine, vitamin B2, vitamin B6, and vitamin B12) was not related to risk of endometrial cancer. No association was observed between endometrial cancer and the MTHFR 677C>T, 1298 A>C, and 1793G>A polymorphisms or derived haplotypes. Among non-users of supplements, however, the 1298C and 1793A alleles were associated with a lower risk of endometrial cancer among women with high dietary folate intake but related to a higher risk among those with low dietary folate intake (P(interaction) = 0.08 and 0.03, respectively). Further analysis showed that the lowest risk (OR, 0.6; 95% CI, 0.4-1.1) was among women with the 1298C allele and the highest intake of both folate and riboflavin (P(interaction) = 0.04). A similar association was observed for the 1793A allele (P(interaction) = 0.03). Our findings suggest that folate intake may decrease the risk of endometrial cancer and modify the effect of MTHFR polymorphisms on risk.

A population‐based case‐control study of endometrial cancer in shanghai, china

A case-control study of 268 patients with endometrial cancer and 268 population controls was conducted during 1988-1990 in Shanghai, China, to evaluate etiologic factors in a population whose risk had not been substantially altered by the use of exogenous estrogens. In spite of this, the major risk factors resembled those found in other studies. The risk of endometrial cancer was significantly elevated among nulligravidas (OR = 5.4, 95% CI = 2.0-14.6) and decreased with number of pregnancies (p less than 0.01). Late age at menopause was associated with increased risk, while early age at menarche was unrelated. Use of oral contraceptives for more than 2 years was associated with a reduction in endometrial cancer risk (OR = 0.4, 95% CI = 0.1-1.2), while short-term use of oral contraceptives and other methods of contraception were unrelated. Obesity was a strong predictor of risk, with women in the highest quartile of weight having 2.5 times the risk of those in the lowest quartile. In contrast to many other studies, cigarette smokers were at elevated risk (OR = 1.7, 95% CI = 0.9-3.0). Risk was also elevated among women reporting a history of gall-bladder disease, polycystic ovaries, menstrual symptoms, and non-estrogen hormone use.