Pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome: a Korean National Health Insurance Service study.

OBJECTIVE: Polycystic ovarian syndrome is associated with diverse pregnancy related complications and endometrial cancer. However, research on the relationship between pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome is scarce. We aimed to examine the association between gestational diabetes mellitus, pregnancy induced hypertension, and preterm birth and the risk of endometrial cancer in women with polycystic ovarian syndrome. METHODS: We analyzed data from the National Health Information Database established by the Korean National Health Insurance Service between January 2002 and December 2019. We included women with gestational diabetes mellitus, pregnancy induced hypertension, preterm birth, and endometrial cancer from among the polycystic ovarian syndrome population. All conditions were diagnosed according to the Korean Informative Classification of Diseases, 10th revision codes. Age, area of residence, income, body mass index, waist circumference, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, fasting blood sugar, and creatinine levels were included as covariates in the multiple logistic regression analysis. RESULTS: Of 467 221 women with polycystic ovarian syndrome included, 5099 had endometrial cancer. Age, residence, income, body mass index, waist circumference, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, fasting blood sugar, and creatinine levels differed significantly between the endometrial cancer and non-endometrial cancer groups (p≤0.001-0.032). Among the polycystic ovarian syndrome population, the odds ratios (ORs) of endometrial cancer were 1.50, 1.43, and 1.23 in women with a history of gestational diabetes mellitus, pregnancy induced hypertension, and preterm birth, respectively, compared with those without a history of these conditions (OR 1.50, 95% confidence interval (CI) 1.32 to 1.69, p<0.001; 1.43, 1.04 to 1.97, p=0.027; and 1.23, 1.05 to 1.45, p=0.011, respectively). CONCLUSION: Our results suggest that a history of pregnancy complications (gestational diabetes mellitus, pregnancy induced hypertension, and preterm birth) increases the risk of endometrial cancer in women with polycystic ovarian syndrome.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Association between coffee drinking and endometrial cancer risk: A meta-analysis.

AIM: Coffee drinking is considered as a risk factor of endometrial cancer (EC). Here, we conducted a meta-analysis of observational study to evaluate the relationship between coffee drinking and the risk of EC. METHODS: The MEDLINE and EMBASE databases were searched until July 2018. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of 24 studies (12 case-control and 12 cohort studies) on coffee intake with 9833 incident cases of EC and 699 234 subjects were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus the lowest categories of coffee intake was 0.71 (95% CI: 0.65-0.77; I2  = 14%, p for heterogeneity = 0.26). By study design, the pooled RRs were 0.68 (95% CI: 0.56-0.83) for case-control studies and 0.70 (95% CI: 0.63-0.77) for cohort studies. For different regions, the pooled RRs were 0.74 (95% CI: 0.62-0.88) in Europe, 0.71 (95% CI: 0.64-0.79) in United States/Canada, and 0.40 (95% CI: 0.28-0.57) in Japan. By additional subgroup analysis, a stronger inverse association was shown in caffeinated coffee drinkers (RR 0.66, 95% CI: 0.52-0.83), individuals with the higher body mass index (BMI) (RR 0.65, 95% CI: 0.54-0.79), never smokers (RR 0.68, 95% CI: 0.56-0.84), ever smokers (RR 0.56, 95% CI: 0.45-0.70), and those who never used hormone replacement therapy (HRT) (RR 0.88, 95% CI: 0.79-0.98). The consumption of filtered or boiled coffee showed no significant association. CONCLUSIONS: Increased coffee intake is associated with a reduced risk of EC.

Tea Consumption and the Risk of Endometrial Cancer: An Updated Meta-Analysis.

Although the relationship between tea consumption and the risk of endometrial cancer has been previously analyzed in certain studies, the resulting information is still conflicting, and a previous meta-analysis yielded inconsistent results. Therefore, here, we aimed to perform an updated meta-analysis of studies on this subject in order to elucidate this relationship.We searched the literature on the PubMed, Web of Science, Scopus, and Chinese National Knowledge Infrastructure databases for studies that were published prior to September 25, 2019, and all the relevant references were examined. Ultimately, we included eight studies, and seven of them were on black tea. We used the overall relative risk values (RR) and 95% confidence intervals (CI) to evaluate the risk. The synthetic RR of the eight eligible studies demonstrated that tea consumption was not relevant to the incidence rate of endometrial cancer (RR 1.06, 95% CI 0.96, 1.18). No publication bias was found. We detected significant heterogeneity among the studies (Q = 15.84, p = 0.027, I2 = 55.8%). In conclusion, the results of this meta-analysis indicate that tea consumption is not relevant to the incidence of endometrial cancer. Further research and cohort studies should be conducted to validate our result.

Coffee drinking and cancer risk: an umbrella review of meta-analyses of observational studies.

BACKGROUND: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. METHODS: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. RESULTS: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. CONCLUSIONS: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

Energy balance related lifestyle factors and risk of endometrial and colorectal cancer among individuals with lynch syndrome: a systematic review.

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to June 14th, 2018. In total, 1060 studies were identified and 16 were included. Three studies were related to EC and 13 to CRC. Overall, evidence suggests that weight status/weight change may not be associated with EC risk and multivitamin and folic-acid supplementation may be associated with decreased EC risk. Early-adulthood overweight/obese weight-status and adulthood weight-gain may be associated with increased CRC risk, whereas multivitamin supplementation, tea and high fruit intake, and physical activity may be associated with decreased CRC risk. Current evidence proposes that recommendations related to weight, some dietary habits, and physical activity recommended for the general public are also relevant to individuals with lynch syndrome. More research is needed, specifically prospective cohorts and randomized controlled trials, to determine if tailored recommendations are needed among individuals with lynch syndrome.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies.

BACKGROUND: Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose-response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. MATERIALS AND METHODS: We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose-response analyses were conducted by using generalized least square trend estimation. RESULTS: We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68-0.81; pheterogeneity = 0.09, I2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71-0.85; pheterogeneity = 0.14, I2 = 31.9%) and 0.63 (95% CI: 0.53-0.76; pheterogeneity = 0.57, I2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2-4%) in cohort studies and 12% (95% CI: 5-18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61-0.81). CONCLUSION: The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.

Tea and coffee and risk of endometrial cancer: cohort study and meta-analysis.

BACKGROUND: Previous reports, mostly from retrospective studies, suggested possible protective effects of both tea and coffee against endometrial cancer, but recent reports from prospective studies generally showed weaker or null associations. OBJECTIVES: We investigated endometrial cancer risk in relation to tea and coffee consumption in a large prospective study and did a meta-analysis of published results. DESIGN: Daily consumption of tea and coffee was recorded in 560,356 participants (without a hysterectomy) in the UK Million Women Study of whom 4067 women developed endometrial cancer during 5.2 million person-years of follow up (average: 9.3 y per woman). RESULTS: With the use of Cox proportional hazards regression, we showed no significant association between endometrial cancer risk and consumption of either tea (multivariate adjusted RR per cup daily: 1.00; 95% CI: 0.98, 1.02) or coffee (RR per cup daily: 0.98; 95% CI: 0.96, 1.01). Our meta-analyses showed no significant association between endometrial cancer risk and tea consumption and a weak association for coffee consumption in prospective studies, but there may have been selective publication of only part of the evidence. CONCLUSIONS: There is little or no association between tea consumption and endometrial cancer risk. If there is any association with coffee consumption, it appears to be weak.

Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

OBJECTIVE: Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. DESIGN: Prospective cohort study. SETTING: Ten public health centre areas in Japan. POPULATION: Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. METHODS: Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). MAIN OUTCOME MEASURE: Incidence of endometrial cancer. RESULTS: During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). CONCLUSION: In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk.

The prescription pattern of Chinese herbal products that contain dang-qui and risk of endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan: a population-based study.

PURPOSE: The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. METHODS: All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort. RESULTS: Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20-79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44-0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55-79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46-1.17). CONCLUSIONS: Dang-qui consumption is common among breast cancer survivors aged 20-79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment.

Associations of long-chain ω-3 fatty acids and fish intake with endometrial cancer risk in the VITamins And Lifestyle cohort.

BACKGROUND: Inflammation plays an important role in endometrial cancer etiology. Long-chain ω-3 (n-3) polyunsaturated fatty acids (PUFAs), derived from marine sources, are thought to be antiinflammatory; however, several studies of fish consumption suggest an increase in risk. OBJECTIVE: This study examined whether intakes of long-chain ω-3 PUFAs, including eicosapentaenoic acid (EPA; 20:5ω-3) and docosahexaenoic acid (DHA; 22:6ω-3), from diet and supplements and intake of fish are associated with endometrial cancer risk. DESIGN: Between 2000 and 2002, 22,494 women aged 50-76 y, living in western Washington State, were recruited to the VITamins And Lifestyle cohort study. Incident endometrial cancers (n = 263) were identified through the Surveillance, Epidemiology, and End Results cancer registry after 9 y of follow-up. Multivariable-adjusted HRs and 95% CIs for the association of intakes of individual long-chain ω-3 PUFAs and fish with endometrial cancer risk were estimated by using Cox proportional hazards. RESULTS: Women in the highest compared with the lowest quintile of dietary EPA + DHA intake had a 79% increased risk of endometrial cancer (95% CI: 16%, 175%; P-trend = 0.026). Results were similar for EPA and DHA measured individually and for fish intake. When data were stratified by body mass index (in kg/m²; <25 or ≥ 25), increases in risk of long-chain ω-3 PUFAs were restricted to overweight and obese women, and statistically significant reductions in risk were observed for normal-weight women. CONCLUSIONS: The overall increased risk reported here confirms the findings of several prior observational studies of fish intake, which observed similar increases in risk. Randomized trials are needed to confirm these findings.

Evaluation of removable statistical interaction for binary traits.

This paper is concerned with evaluating whether an interaction between two sets of risk factors for a binary trait is removable and, when it is removable, fitting a parsimonious additive model using a suitable link function to estimate the disease odds (on the natural logarithm scale). Statisticians define the term 'interaction' as a departure from additivity in a linear model on a specific scale on which the data are measured. Certain interactions may be eliminated via a transformation of the outcome such that the relationship between the risk factors and the outcome is additive on the transformed scale. Such interactions are known as removable interactions. We develop a novel test statistic for detecting the presence of a removable interaction in case-control studies. We consider the Guerrero and Johnson family of transformations and show that this family constitutes an appropriate link function for fitting an additive model when an interaction is removable. We use simulation studies to examine the type I error and power of the proposed test and to show that, when an interaction is removable, an additive model based on the Guerrero and Johnson link function leads to more precise estimates of the disease odds parameters and a better fit. We illustrate the proposed test and use of the transformation by using case-control data from three published studies. Finally, we indicate how one can check that, after transformation, no further interaction is significant.

Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case-control study.

PURPOSE: Animal and laboratory studies suggest that long-chain omega-3 (n-3) fatty acids, a type of polyunsaturated fat found in fatty fish, may protect against carcinogenesis, but human studies on dietary intake of polyunsaturated fats and fish with endometrial cancer risk show mixed results. METHODS: We evaluated the associations between endometrial cancer risk and intake of fatty acids and fish in a population-based sample of 556 incident cancer cases and 533 age-matched controls using multivariate unconditional logistic regression methods. RESULTS: Although total n-3 fatty acid intake was not associated with endometrial cancer risk, higher intakes of eicosapentaenoic (EPA 20:5) and docosahexaenoic (DHA 22:6) fatty acids were significantly associated with lower risks (OR = 0.57, 95 % CI: 0.39-0.84; OR = 0.64, 95 % CI: 0.44-0.94; respectively) comparing extreme quartiles. The ratio of n-3:n-6 fatty acids was inversely associated with risk only on a continuous scale (OR = 0.84, 95 % CI: 0.71-0.99), while total fish intake was not associated with risk. Fish oil supplement use was significantly associated with reduced risk of endometrial cancer: OR = 0.63 (95 % CI: 0.45-0.88). CONCLUSIONS: Our results suggest that dietary intake of the long-chain polyunsaturated fatty acids EPA and DHA in foods and supplements may have protective associations against the development of endometrial cancer.

A prospective investigation of coffee drinking and endometrial cancer incidence.

Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50-71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51-0.80; P(trend) = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86-0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87-0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (P(interaction) = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41-0.72; P(trend) = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.

Legume, soy, tofu, and isoflavone intake and endometrial cancer risk in postmenopausal women in the multiethnic cohort study.

BACKGROUND: Phytochemicals found in soy and other legumes have been speculated to reduce the risk of endometrial cancer; however, inconsistent findings have been reported in the few epidemiological studies conducted to date. METHODS: We conducted a prospective analysis of 46 027 nonhysterectomized postmenopausal women who were recruited into the Multiethnic Cohort (MEC) Study between August 1993 and August 1996 and provided detailed baseline information on diet and other endometrial cancer risk factors. A total of 489 women diagnosed with incident endometrial cancer were identified through the Surveillance, Epidemiology, and End Results tumor registry linkages during a median follow-up period of 13.6 years. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with dietary intake of legumes, soy, and tofu, and for total isoflavones and specific isoflavones (daidzein, genistein, or glycitein). Truncated (age 50-89 years) age-adjusted incidence rates were calculated by applying age-specific rates within isoflavone quintiles to the overall MEC population eligible for endometrial cancer. To estimate the percentage of endometrial cancers that may have been prevented by consuming the highest quintile of total isoflavones, the partial population attributable risk percent was calculated. RESULTS: A reduced risk of endometrial cancer was associated with total isoflavone intake (highest vs lowest quintile, ≥7.82 vs <1.59 mg per 1000 kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91), daidzein intake (highest vs lowest quintile, ≥3.54 vs <0.70 mg per 1000 kcal/d, RR = 0.64, 95% CI = 0.46 to 0.90), and genistein intake (highest vs lowest quintile, ≥3.40 vs <0.69 mg per 1000 kcal/d, RR = 0.66, 95% CI = 0.47 to 0.91). No statistically significant association with endometrial cancer risk was observed for increasing intake of legumes, soy, tofu, or glycitein. Truncated age-adjusted incidence rates of endometrial cancer for the highest vs lowest quintile of total isoflavone intake were 55 vs 107 per 100 000 women per year, respectively. The partial population attributable risk percent for total isoflavone intake lower than the highest quintile was 26.7% (95% CI = 5.3% to 45.8%). CONCLUSION: This study suggests that greater consumption of isoflavone-containing foods is associated with a reduced risk of endometrial cancer in this population of nonhysterectomized postmenopausal women.

Risk of endometrial cancer in relation to individual nutrients from diet and supplements.

OBJECTIVE: Intake of nutrients may influence the risk of endometrial cancer (EC). We aimed to estimate the association of intake of individual nutrients from food and from food plus supplements with EC occurrence. DESIGN: A population-based case-control study conducted in Canada (2002-2006). SETTING: Nutrient intakes from food and supplements were assessed using an FFQ. Logistic regression was used to estimate EC risk within quartile levels of nutrient intakes. SUBJECTS: Incident EC cases (n 506) were identified from the Alberta Cancer Registry, and population controls were frequency- and age-matched to cases (n 981). RESULTS: There existed little evidence of an association with EC for the majority of macronutrients and micronutrients examined. We observed a statistically significant increased risk associated with the highest, compared with the lowest, quartile of intake of dietary cholesterol (multivariable-adjusted OR = 1·51, 95 % CI 1·08, 2·11; P for trend = 0·02). Age-adjusted risk at the highest level of intake was significantly reduced for Ca from food sources (OR = 0·73, 95 % CI 0·54, 0·99) but was attenuated in the multivariable model (OR = 0·82, 95 % CI 0·59, 1·13). When intake from supplements was included in Ca intake, risk was significantly reduced by 28 % with higher Ca (multivariable-adjusted OR = 0·72, 95 % CI 0·51, 0·99, P for trend = 0·04). We also observed unexpected increased risks at limited levels of intakes of dietary soluble fibre, vitamin C, thiamin, vitamin B6 and lutein/zeaxanthin, with no evidence for linear trend. CONCLUSIONS: The results of our study suggest a positive association between dietary cholesterol and EC risk and an inverse association with Ca intake from food sources and from food plus supplements.

Overview of long term care of breast cancer survivors.

Breast cancer, the most common cancer in women in developed countries, has a generally excellent prognosis, therefore long-term survivors living with the consequences of breast cancer ('survivors') and its treatment are an increasing group in clinical practice. This review discusses the complex issues relevant to survivorship care, including current recommendations for ongoing adjuvant hormonal therapy (tamoxifen and aromatase inhibitors), and the management of side effects of cancer treatment (such as menopause, arthralgia, and lymphoedema). Annual mammography screening is advised for detection of second breast cancers, and symptom-directed assessment is warranted where there is suspicion of distant recurrence or (in women using tamoxifen) of endometrial cancer. Management of menopausal symptoms, including treatment-induced premature menopause, is a key issue for many survivors, and can be challenging to manage as conventional hormone replacement therapy is contraindicated in most of these women. Specific therapeutic options for hot flushes and vaginal symptoms are discussed. The review also emphasises the need for survivorship care to include optimisation of general health, including psychosocial and sexual health, bone health and the evaluation of lifestyle-related risk factors and genetic factors. The review provides guidance on the management of many of these issues, and highlights areas requiring further evidence and research.