Dietary fat intake and endometrial cancer risk

AbstractSince body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case–control studies were included. Pooled analysis of case–control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001).  studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73–0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case–control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk.

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title: Type I and II endometrial cancers: have they different risk factors?
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title: Effect of Dietary Fat and Omega-3 Fatty Acids on Urinary Eicosanoids and Sex Hormone Concentrations in Postmenopausal Women: A Randomized Controlled Feeding Trial
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title: Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women
abstract: AbtractObjectiveEndogenous sex hormones have been implicated in the etiology of breast cancer. Dietary factors such as fat, dietary fiber, soy isoflavones, and alcohol have been suggested to influence endogenous estrogen and other steroid hormone levels. We examined the relationship among these dietary factors and plasma sex hormone levels in premenopausal Japanese women.MethodsWe measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, a follicle-stimulating hormone, a luteinizing hormone, and prolactin among 393 premenopausal women who had regular menstrual cycles fewer than 40 days apart. The dietary intakes were estimated with a validated food frequency questionnaire.ResultsAfter controlling for age, BMI, phase of the menstrual cycle, number of births, age at first birth, history of breastfeeding, and smoking status, the saturated fat intake was significantly positively associated with total estradiol and free estradiol levels. Intakes of the other types of fat, dietary fiber, soy isoflavones, and alcohol were not significantly associated with levels of any hormone measured.ConclusionsThese data suggest that a high intake of saturated fat is associated with increased estradiol levels in premenopausal Japanese women. Saturated fat intake may have implications in the etiology of breast cancer.

title: High saturated fatty acid intake induces insulin secretion by elevating gastric inhibitory polypeptide levels in healthy individuals.
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title: Inflammation and Endometrial Cancer: A Hypothesis
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title: Metabolic syndrome and risk of cancer: which link?
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title: Dietary lipids and endometrial cancer: the current epidemiologic evidence
abstract: BackgroundBecause dietary fat has been postulated to affect obesity and estrogen levels, two important risk factors for endometrial cancer, its association with this disease has received some attention. We summarize here the current evidence for several dietary lipids.MethodsSearches were conducted to identify peer-reviewed manuscripts up to December 2006. Two cohort studies and nine case–control studies were included in meta-analyses.ResultsRandom-effects summary estimates for case–control studies were 1.24 (95% CI: 1.10, 1.41) per 10% kcal from total fat and 1.28 (95% CI: 1.12, 1.47) per 10 g/1,000 kcal of saturated fat. The only cohort study evaluating total fat and saturated fat did not find an association. We estimated a 35% increased risk (95% CI: 0.96, 1.90) per 150 mg/1,000 kcal of cholesterol intake, based on six case–control studies. For animal fat (per 10 g/1,000 kcal) the summary estimates were 0.78 (95% CI: 0.63, 0.96) and 1.34 (95% CI: 1.06, 1.69) for two cohort and four case–control studies, respectively.ConclusionsCase–control data suggest an increased risk for total, saturated, and animal fat. However, the limited available cohort data do not support these associations. Additional data, particularly from prospective studies, are needed before conclusions can be drawn.

title: A cohort study of nutritional factors and endometrial cancer
abstract: To evaluate the role of nutritional factors in the etiology of endometrial cancer, we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a subcohort was constructed by selecting a 10% random sample from the 56,837 women in the dietary cohort. Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31, 1993 and ascertained by record linkage to the Canadian Cancer Database. Information on usual diet at enrolment and other epidemiological variables was collected by means of self-administered questionnaires. Hazard ratios were obtained from proportional hazards regression models, with estimation of robust standard errors. We found a strong association of endometrial cancer with body mass index >25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06–3.50). Endometrial cancer risk was not associated significantly with intakes of total energy, carbohydrates, proteins, total fat and major fatty acids, total dietary fiber and various types of fibers, vitamin C, E and A, folic acid, β-carotene, lutein, or cryptoxanthin. Some decrease in risk was noted with relatively high intakes of saturated fat, animal fat or lycopene. The associations observed in the study were independent of total energy intake and most non-dietary risk factors. The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women.

title: Metabolic abnormalities (hypertension, hyperglycemia and overweight), lifestyle (high energy intake and physical inactivity) and endometrial cancer risk in a Norwegian cohort
abstract: Since high energy intake, inactivity, hypertension and diabetes are linked to obesity and an unfavorable hormonal profile, we wanted to test whether energy intake, physical activity, blood pressure and serum glucose are related to the risk of endometrial cancer independent of the body mass index (BMI). A cohort of 24,460 women, aged 20–49 years, attended a Norwegian health screening twice during 1974–1981; they answered questions about diet, physical activity and chronic diseases, and their height, weight, blood pressure and non‐fasting serum glucose were measured. By the end of 1996, during 15.7 years of follow‐up, 130 cases of endometrial carcinomas were identified. The relative risks (RRs) for endometrial cancer were estimated in proportional hazards models including potentially confounding factors. Obese women (BMI ≥ 30 kg/m2) were at 2.6 times increased risk of endometrial cancer compared to normal weight women (BMI < 25 kg/m2) (RR = 2.57, 95%CI = 1.61–4.10). Among overweight women (BMI ≥ 25 kg/m2), non‐fasting serum glucose in the upper quartile vs. in the lower quartile was associated with a 2.4 times increase in risk (RR = 2.41, 95%CI = 1.08–5.37), whereas among obese women, blood pressure above 140/90 mmHg vs. below 140/90 mmHg in both surveys was associated with a 3.5 times increase in risk (RR = 3.47, 95%CI = 1.24–9.70). Especially in women younger than 50 years, high energy intake (5,044–6,401 kJ/day) conferred higher risk compared to low energy intake (< 4266 kJ/day) (RR = 3.40, 95%CI = 1.52–7.60). Increasing recreational activity tended to be protective. Among obese women with non‐sedentary jobs at both screenings, RR declined to 0.18 (95%CI = 0.05–0.62) as the level of sustained occupational activity increased (ptrend = 0.03). Our results suggest that inactivity and high energy intake are major risk factors for endometrial cancer independent of BMI, and that hypertension and relative hyperglycemia are significant markers of risk, especially among the heaviest women.

title: Dietary Fat, Fiber, and Carbohydrate Intake in Relation to Risk of Endometrial Cancer
abstract: Macronutrients such as fat and fiber have been hypothesized to play a role in the etiology of endometrial cancer.  To investigate these associations, the authors analyzed data from the Nurses' Health Study. From 1980 to 2006, 669 invasive adenocarcinoma cases were identified over 1.3 million person-years of follow-up. Dietary intake was assessed in 1980 and updated every 2–4 years. Cox proportional hazard models were used to calculate relative risks (RRs), controlling for total energy and other risk factors.  Overall, the authors found no significant associations between most dietary factors and endometrial cancer risk. Total fat was associated with a borderline significant decreased risk (top vs. bottom quintile RR = 0.78; 95% CI = 0.60–0.99; Ptrend = 0.18). Findings for animal fat were similar. No inverse associations between dietary fibers and cancer risk were observed. Cereal fiber was modestly positively associated with risk (top vs. bottom quintile RR = 1.38, 95% CI = 1.07–1.79; Ptrend = 0.05). The inverse association with animal fat intake and a positive association with carbohydrate intake were observed among premenopausal but not among postmenopausal women.  In this large prospective study, no overall association was observed between dietary fat, fiber, and carbohydrates with endometrial cancer risk, although several of the relationships may vary by menopausal status.  Dietary fat and fiber intake do not seem to play a major role in endometrial cancer etiology overall. However, further evaluation of these associations, particularly in premenopausal women, is needed. Cancer Epidemiol Biomarkers Prev; 20(5); 978–89.

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



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.



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.



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.



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.

title: Dietary associations in a case-control study of endometrial cancer
abstract: Despite the established role of obesity in the etiology of endometrial cancer, limited data are available from analytical epidemiologic studies on the association of risk with dietary factors. A case-control study of 399 cases and 296 controls conducted in five areas of the United States from 1 June 1987 to 15 May 1990, enabled evaluation of risk related to dietary intakes adjusted for potential confounders. Caloric intake was associated modestly with increased risk (odds ratio [OR]=1.5,95 percent confidence interval [CI]=0.9–2.5 for highest cf lowest quartiles of intake), with the principal contributors being fat and protein calories. After adjustment for other risk factors, including body mass, increased risk was associated with higher intakes of fat. Several components of fat investigated were associated with increased risk, although associations were slightly stronger for saturated fat (OR=2.1, CI=1.2–3.7) and oleic acid (OR=2.2, CI=1.2–4.0) than for linoleic acid (OR=1.6, CI=0.9–2.8). Food-group analyses showed intake of complex carbohydrates—and specifically of breads and cereals—associated with reduced risks (OR=0.6, CI=0.4–1.1), whereas animal fat and fried foods were associated with elevated risks (OR=1.5 and 1.7, respectively). The relations of endometrial cancer with animal fat and complex carbohydrates were independent. No consistent associations were noted for intakes of cholesterol, fiber, vitamins A and C, individual carotenoids, or folate-rich foods. These data imply an etiologic role for a diet rich in total fat and/or animal fat and low in complex carbohydrates with endometrial cancer. These associations are consistent with a hormonal mechanism and were independent of the associations of obesity and other risk factors.

title: Diet, body size, physical activity, and the risk of endometrial cancer.
abstract: Endometrial cancer is associated with increased weight and body size, diabetes, and other conditions that may result from an excess in calories or lack of physical activity. Although a few studies have explored the effect of dietary constituents on the risk of endometrial cancer, the nature of the joint association of these constituents and obesity, energy intake, or energy expenditure with risk is unknown. A population-based case-control study was conducted in Hawaii to examine the association of diet, body size, and physical activity with the risk of endometrial cancer. Subjects included 332 histologically confirmed, primary endometrial cancer cases and 511 controls identified between 1985 and 1993. Cases and controls were residents of Oahu, Hawaii who were between 18 and 84 years of age and were from one of the following ethnic groups: Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese. Cases were identified through the Hawaii Tumor Registry and matched to the controls on age (+/-2.5 years) and ethnicity. In-person interviews, conducted in the subjects' homes, included dietary, reproductive, menstrual, and medical histories and use of exogenous hormones, physical activity, and other lifestyle variables. Weight, girth, and skinfold measurements were taken at the time of the interview. We found a strong dose-response relation of increased body size to the development of endometrial cancer after adjustment for energy intake. The odds ratio (OR) for endometrial cancer among women in the highest quartile of body mass index (BMI; kg/m2) was more than four times that among women in the lowest quartile. Waist, hip, midarm, and wrist girths were positively associated with the estimated risk of endometrial cancer after adjustment for total calories and other nondietary risk factors, although the trends in the ORs were attenuated after adjustment for BMI. Physically active women had a modest reduction in their risk of disease compared with inactive women. Cases consumed a greater percentage of their calories from fat and a lower percentage of their calories from carbohydrates than did controls. Adjustment for BMI reduced the ORs for the highest compared with the lowest quartile of fat calorie intake from 2.0 (95% confidence interval, 1.3-3.2) to 1.6 (95% confidence interval, 1.0-2.6), suggesting that part of the association is explained by obesity. There was a differential effect of fat on endometrial cancer according to BMI. For all components of fat, the associations with endometrial cancer were either minimal or absent among leaner women (i.e., those with BMI below the median), whereas, among more obese women, two-fold differences in risk were observed between women above and below the median of fat intake. Foods that are high in fat and cholesterol, such as red meat, margarine, and eggs, were positively associated with endometrial cancer, whereas cereals, legumes, vegetables, and fruits, particularly those high in lutein, were inversely associated. These findings suggest that women who avoid being overweight and who consume a diet low in plant and animal fats and high in complex carbohydrates are at a reduced risk of endometrial cancer.

title: Diet in the epidemiology of endometrial cancer in Western New York (United States)
abstract: We examined diet and risk of endometrial cancer among women in the Western New York Diet Study (1986–1991).
 Self-reported frequency of use of 172 foods and beverages during the 2 years before the interview and other relevant data were collected by detailed interviews from 232 endometrial cancer cases and 639 controls, frequency-matched for age and county of residence. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education, body mass index (BMI), smoking history, hypertension, diabetes, age at menarche, parity, oral contraceptive use, menopausal status, menopausal estrogen use, and energy.
 Risks were reduced for women in the highest quartiles of intake of protein (OR 0.4, 95% CI: 0.2–0.9), dietary fiber (OR 0.5, 95% CI: 0.3–1.0), phytosterols (OR 0.6, 95% CI: 0.3–1.0), vitamin C (OR 0.5, 95% CI: 0.3–0.8) folate (OR 0.4, 95% CI: 0.2–0.7), alpha-carotene (OR 0.6, 95% CI: 0.4–1.0), beta-carotene (OR 0.4, 95% CI: 0.2–0.6), lycopene (OR 0.6, 95% CI: 0.4–1.0), lutein + zeaxanthin (OR 0.3, 95% CI: 0.2–0.5) and vegetables (OR 0.5, 95% CI: 0.3–0.9), but unrelated to energy (OR 0.9, 95% CI: 0.6–1.5) or fat (OR 1.6, 95% CI: 0.7–3.4).
 Our results support previous findings of reduced endometrial cancer risks associated with a diet high in plant foods.

title: The association of dietary fat and plant foods with endometrial cancer (United States)
abstract: To examine the associations of dietary fat and selected plant foods with endometrial cancer in a population-based case–control study.
 Six hundred and seventy-nine incident cases of endometrial cancer diagnosed between 1985 and 1991, and 944 population-based controls completed a 98-item semi-quantitative food-frequency questionnaire and a detailed in-person interview which collected information on endometrial cancer risk factors. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of endometrial cancer, adjusted for age, county, energy intake, hormone use, smoking and, in separate models, for body mass index (BMI: kg/m2).
 Percent energy from fat was associated with an increased risk of endometrial cancer (highest quintile cf. lowest: OR = 1.8, 95% CI 1.3–2.6), with saturated and monounsaturated fats being the main contributors of risk. There was a stronger association between dietary fat and endometrial cancer among groups with higher circulating estrogen levels (i.e. women with higher BMI, users of unopposed estrogens, non-smokers, and younger age at menarche). Consumption of fruits or vegetables was inversely associated with endometrial cancer risk (highest quintile cf. lowest: OR = 0.65, 95% CI 0.46–0.93 and OR = 0.61, 95% CI 0.43–0.88, respectively). Further adjustment for BMI resulted in little or no attenuation of the ORs and associated CIs.
 These results provide support for the theory that a low-fat, high-fruit and high-vegetable diet may reduce the risk of endometrial cancer, and that these dietary factors may act independently of the effect of BMI.

title: Nutritional factors in relation to endometrial cancer: A report from a population‐based case‐control study in Shanghai, China
abstract: We evaluated the role of dietary nutrients in the etiology of endometrial cancer in a population‐based case‐control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency‐matched controls. Information on usual dietary habits was collected during an in‐person interview using a validated, quantitative food frequency questionnaire. Logistic regression analysis was conducted to evaluate the association of nutrients with endometrial cancer risk using an energy density method (e.g., nutrient intake/1,000 kilocalories of intake). Higher energy intake was associated with increased risk, which was attributable to animal source energy and a high proportion of energy from protein and fat. Odds ratios comparing highest versus lowest quintiles of intake were elevated for intake of animal protein (Odds ratio (OR) = 2.0, 95% confidential interval: 1.5–2.7) and fat (OR = 1.5, 1.2–2.0), but reduced for plant sources of these nutrients (OR = 0.7, 0.5–0.9 for protein and OR = 0.6, 0.5–0.8 for fat). Further analysis showed that saturated and monounsaturated fat intake was associated with elevated risk, while polyunsaturated fat intake was unrelated to risk. Dietary retinol, β‐carotene, vitamin C, vitamin E, fiber, and vitamin supplements were inversely associated with risk. No significant association was observed for dietary vitamin B1 or vitamin B2. Our findings suggest that associations of dietary macronutrients with endometrial cancer risk may depend on their sources, with intake of animal origin nutrients being related to higher risk and intake of plant origin nutrients related to lower risk. Dietary fiber, retinol, β‐carotene, vitamin C, vitamin E, and vitamin supplementation may decrease the risk of endometrial cancer.

title: Higher intakes of vegetables and vegetable-related nutrients are associated with lower endometrial cancer risks.
abstract: A limited number of studies have investigated diet in association with endometrial cancer (EC). We examined the association between intakes of selected food groups and nutrients with EC risk among 541 women with histologically confirmed EC and 541 women with an intact uterus and noncancer diagnoses seen at Roswell Park Cancer Institute between 1982 and 1998. Self-reported dietary and other epidemiologic data were collected by questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% CI, adjusting for age, BMI, hormone replacement therapy use, cigarette smoking, lifetime duration of menstruation, and total energy intake. We observed significant inverse associations for women in the highest vs. lowest quartiles of intake of total vegetables (OR, 0.51; 95% CI, 0.34-0.75), vitamin E (OR, 0.44; 95% CI, 0.27-0.70), dietary fiber (OR, 0.60; 95% CI, 0.39-0.94), beta-carotene (OR, 0.55; 95% CI, 0.37-0.82), lutein (OR, 0.52; 95% CI, 0.34-0.78), and folate (OR, 0.57; 95% CI, 0.36-0.91). Our results support that vegetables and related nutrients are associated with decreased risk of EC.

title: Risk of endometrial cancer in relation to individual nutrients from diet and supplements
abstract: 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.  A population-based case–control study conducted in Canada (2002–2006).  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).  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.  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.

title: Omega-3 and omega-6 fatty acid intakes and endometrial cancer risk in a population-based case–control study
abstract: PurposeAnimal 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.MethodsWe 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.ResultsAlthough 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).ConclusionsOur 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.

title: Dietary factors and the risk of endometrial cancer: a case--control study in Greece.
abstract: In a hospital-based case-control study of endometrial cancer undertaken in Athens (1992-94), 145 women residents of Greater Athens with confirmed cancer of the endometrium were compared with 298 control patients with orthopaedic diseases. Personal interviews were conducted in the hospital setting, and diet was assessed using a validated semiquantitative food frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient intake of a typical portion size for each specified food item by the frequency at which the food was consumed per month and summing these estimates for all food items. Data were modelled through logistic regression, controlling for demographic, reproductive and somatometric risk factors for endometrial cancer as well as for total energy intake. No macronutrient was significantly associated with endometrial cancer risk, but increasing intake of monounsaturated fat, mostly olive oil, by about one standard deviation was associated with a 26% risk reduction (odds ratio = 0.74; 95% confidence interval 0.54-1.3). Among micronutrients, only calcium intake was significantly inversely associated with endometrial cancer risk, whereas there was evidence against retinol and zinc imparting protection against the disease. With respect to food groups, there was weak and non-significant evidence that vegetables are protective, whereas consumption of pulses was positively associated with disease possibly because they contribute substantially in Greece to energy intake in excess of physical activity-dependent requirements.

title: Dietary factors and endometrial cancer risk. Results of a case–control study in Mexico
abstract: Daily diet factors that could potentially be related to endometrial cancer (EC) in Mexico are still unknown. This study aims to evaluate the association between EC and Mexican dietary factors. A case-control study in Mexico City was conducted during 1995–1997 in a social security hospital, using 85 incident cases of EC and 629 controls. A validated questionnaire with 116 items about the frequency and type of food intake was used. The analysis of nutrients was performed using the residual method, adjusting by predictor variables through logistic regression methods. In addition, partitional models estimated total caloric intake for other sources. We found no association between EC risk and consumption of animal or vegetable proteins, saturated, monounsaturated, or polyunsaturated fat, although high intake of nutrients such as lactose (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.21–1.01, P for trend = 0.004), vitamin D (OR, 0.38; 95% CI, 0.18–0.82, P = 0.003), and calcium (OR, 0.39; 95% CI, 0.17–0.89, P = 0.02) were inversely associated with EC. Our results suggest that dietary vitamin D and calcium play an important role in the development of EC, although the mechanisms postulated should be explained with additional studies with large populations.

title: Macronutrients, fatty acids and cholesterol intake and endometrial cancer.
abstract: There is some evidence that dietary habits may influence the risk of endometrial cancer independently of body mass, although the role of diet on endometrial carcinogenesis is unclear.



We carried out a multicenter case-control study from 1992 to 2006 in Italy on 454 women with incident, histologically confirmed endometrial cancer (age range 18-79 years) and 908 controls (age range 19-79 years) admitted to hospitals for acute, non-neoplastic diseases. A validated food-frequency questionnaire was used to estimate macronutrients, fatty acids and cholesterol intake. Logistic regression models, conditioned on age and study centre, and adjusted for major known risk factor of endometrial cancer and residual of energy intake were used to estimate odds ratios (OR) and 95% confidence intervals (CI).



Significant direct associations were observed with intake of energy (OR = 1.7 for the highest versus the lowest quintile, 95% CI = 1.1-2.5), and cholesterol (OR = 2.1, 95% CI = 1.4-3.2), while a direct borderline association emerged with saturated fatty acids (OR = 1.3, 95% CI = 0.9-2.0). There was no association with proteins, sugars, starch, total fat and other selected fatty acids.



Energy and cholesterol intake were associated with endometrial cancer.

title: Association of soy and fiber consumption with the risk of endometrial cancer.
abstract: The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer. These dietary associations may explain in part the reduced rates of uterine cancer in Asian countries compared with those in the United States.

title: Cross-sectional study on relationship between fat intake and malignant cancers in adult women in urban Shanghai
abstract: To investigate the relationship between fat intake and the prevalence of malignant cancers in adult women in urban Shanghai. The data about the fat intake and social demographic factors were collected from the baseline survay on 74 942 participants of the cohort in the Shanghai Women's Health Study(SWHS).In addition to the descriptive analysis,unconditional logistic regression model was used to estimate the odds ratio(OR) of daily intake of fat for some malignant cancers.The median and mean values of fat intake per person per day are 27.40(20.43-35.97) g and(29.46±13.41) g,respectively.The daily intake of fat was associated with the prevalence of all malignant cancers particularly breast,stomach,colon and endometrium cancers.The OR(95% CI) values for the group with highest fat intake were 2.23(95% CI: 1.83-2.70),2.31(95% CI: 1.69-3.17),3.03(95% CI: 1.43-6.43),2.14(95% CI: 0.98-4.67) and 3.14(95% CI: 1.22-8.08) compared with that of the group with lowest fat intake,respectively.The difference was significant.There were no significant differences in the association of fat intake with the corresponding OR values of lung,rectum and thyroid cancer.But trend analysis showed that the risks had an increasing trend with the increase in the fat intake.The positive association is observed between the fat intake and prevalence of all cancers and breast cancer in adult women in urban Shanghai.

title: Adherence to the dietary guidelines for Americans and endometrial cancer risk
abstract: The Healthy Eating Index (HEI) was developed by the US Department of Agriculture with the goal of quantifying adherence to the Dietary Guidelines for Americans. The purpose of this study was to evaluate the impact of the HEI-2005 score and each of its components on endometrial cancer risk in a population-based case–control study in New Jersey. A total of 424 cases and 398 controls completed a Food Frequency Questionnaire, which was used to derive the HEI-2005 score. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression while adjusting for potential covariates, which included all major endometrial cancer risk factors. The adjusted OR for women in the highest quartile when compared to the lowest quartile was 0.83 (95% CI: 0.52–1.34). For the meat and beans component comprising meat, eggs, poultry, fish, and beans, the OR was 0.70 (95% CI: 0.45–1.11; p for trend: 0.07), with little evidence of an association with any of the individual foods. There was no indication of an association for any of the other components of the HEI or of effect modification by body mass index. This study suggested limited value for the HEI-2005 in predicting endometrial cancer risk.

title: Case-control study of endogenous steroid hormones and endometrial cancer.
abstract: It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly.



We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors.



The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases were newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects > or = 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided.



High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E2), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E2 were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones.



High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate.



Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease.

title: Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII
abstract: Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a “nutrient-wide association study” approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR ≤ 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68–0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70–0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. Cancer Epidemiol Biomarkers Prev; 24(2); 466–71.

title: Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women's Health Initiative.
abstract: Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk.



We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype.



Women were n = 87,360 participants of the Women's Health Initiative Observational Study and Clinical Trials who were aged 50-79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk.



Intakes of individual LCω-3PUFAs were associated with 15-23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m(2)) <25, those in the upper compared with lowest quintiles of total LCω-3PUFA intake (sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) had significantly reduced endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers.



Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that use biomarkers of ω-3 intake are needed to more accurately estimate their effects on endometrial cancer risk.

title: Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.
abstract: We study recently developed nonparametric methods for estimating the number of missing studies that might exist in a meta-analysis and the effect that these studies might have had on its outcome. These are simple rank-based data augmentation techniques, which formalize the use of funnel plots. We show that they provide effective and relatively powerful tests for evaluating the existence of such publication bias. After adjusting for missing studies, we find that the point estimate of the overall effect size is approximately correct and coverage of the effect size confidence intervals is substantially improved, in many cases recovering the nominal confidence levels entirely. We illustrate the trim and fill method on existing meta-analyses of studies in clinical trials and psychometrics.

title: Methods for trend estimation from summarized dose-response data, with applications to meta-analysis.
abstract: Meta-analysis often requires pooling of correlated estimates to compute regression slopes (trends) across different exposure or treatment levels. The authors propose two methods that account for the correlations but require only the summary estimates and marginal data from the studies. These methods provide more efficient estimates of regression slope, more accurate variance estimates, and more valid heterogeneity tests than those previously available. One method also allows estimation of nonlinear trend components, such as quadratic effects. The authors illustrate these methods in a meta-analysis of alcohol use and breast cancer.

title: Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form.
abstract: A major problem in reviewing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways. The purpose of this paper is to exemplify methods by which results expressed either as risks (or rates) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner, as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study. An important assumption of the methods is that the quantitative variable has an approximately normal distribution, and a way of investigating the appropriateness of this assumption is given. The methods can be applied to both prospective and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality. In some applications, these methods can be used as a precursor to formal meta-analysis, for example, when differential control of potential confounding factors is not a problem. At the least, the methods can be useful either in quantitatively reviewing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones.

title: An overview of the modulatory effects of oleic acid in health and disease.
abstract: Evidences in the last years have showed the effects of oleic acid (OA) in human health and disease. Olive oil, rich in oleic acid, is supposed to present modulatory effects in a wide physiological functions, while some studies also suggest a beneficial effect on cancer, autoimmune and inflammatory diseases, besides its ability to facilitate wound healing. Although the OA role in immune responses are still controversial, the administration of olive oil containing diets may improve the immune response associated to a more successful elimination of pathogens such as bacteria and fungi, by interfering in many components of this system such as macrophages, lymphocytes and neutrophils. Then, novel putative therapies for inflammatory and infectious diseases could be developed based on the characteristics presented by unsaturated fatty acids like OA. Finally, the purpose of this work was to review some of the modulatory effects of OA on inflammatory diseases and health, aiming at high lightening its potential role on the future establishment of novel therapeutic approaches for infections, inflammatory, immune, cardiovascular diseases or skin repair based on this fatty acid mainly found in the Mediterranean diet.

title: The Association Between Different Kinds of Fat Intake and Breast Cancer Risk in Women
abstract: So far several animal and case-control studies have confirmed this hypothesis that dietary fat increases the risk of breast cancer. However, cohort studies have not shown this relationship. The aim of this study was to review the studies on the relationship between dietary fat intake and breast cancer risk among women. Electronic database PubMed and Google Scholar were searched using the key words: Breast cancer, dietary fat, serum estrogen, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). The evidence of the studies regarding to the association of total and subtypes of fat intake with breast cancer risk are inconsistent. Several studies have shown that, among several types of fat, SFAs and w-3 PUFA intake are associated with an increased and reduced risk of breast cancer, respectively. The relationship between MUFAs intake and breast cancer risk is conflicting. Narrow ranges of fat intake among populations, measurement errors, high correlation between specific types of dietary fat, the confounding variables like body fatness and high-energy intake and other dietary components such as fiber and antioxidants might be probable explanations for these inconsistent results. Although we are not at a stage where we can justifiably advise women to reduce their fat intake to decrease the risk of developing breast cancer, it seems the current guidelines to lower total fat consumption and recommendation to consumption of unsaturated fats such as MUFAs and w-3 fatty acids and also reduction of SFAs (meat and dairy products) intake to avoid heart disease is also useful for breast cancer risk.

title: The role of olive oil in disease prevention: a focus on the recent epidemiological evidence from cohort studies and dietary intervention trials
abstract: Consumption of olive oil within the Mediterranean diet has been long known to have many health benefits. However, only over the last decade has epidemiological research confirmed its protective role against developing several chronic diseases. The objective of this review was to give an overview of the state of art epidemiological evidence concerning the relationship between olive oil and key public health outcomes including mortality, CVD, diabetes, metabolic syndrome (MetS), obesity and cancer, with a particular focus on recent results from cohort studies and dietary intervention trials. Recent epidemiological research has shown that regular consumption of olive oil is associated with increased longevity. This benefit is partly due to the olive oil's unequivocal cardio-protective role. There is converging evidence on the benefits of olive oil for preventing several CVD risk factors, including diabetes, MetS and obesity. Olive oil is also implicated in preventing certain cancers, with the most promising findings for breast and digestive tract cancers, although the data are still not entirely consistent and mainly from case–control studies. These health benefits are supported by strong mechanistic evidence from experimental studies, demonstrating that specific components of olive oil have antihypertensive, antithrombotic, antioxidant, antiinflammatory and anticarcinogenic action. Despite the accumulating epidemiological research, there is still a lack of consistent results from high-quality studies for many health outcomes (i.e. certain cancers and metabolism-related disorders). Further research is mandatory, above all from prospective studies and randomised dietary intervention trials when feasible, to confirm some of the still potential health benefits.

title: Association of dietary and life-style factors with sex hormones in postmenopausal women.
abstract: We examined the relations between endogenous sex hormones and alcohol intake, dietary constituents, and life-style factors in a population-based sample of 253 postmenopausal women not using replacement hormones. Estrone, dihydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), and free and total testosterone were measured in serum. Age and years since menopause were negatively associated with dihydroepiandrosterone sulfate and positively associated with sex hormone-binding globulin levels. Higher relative weight was strongly and negatively associated with sex hormone-binding globulin. Other factors were only very weakly associated with sex hormones. Since, except for weight, few potentially modifiable factors appear to influence these hormone profiles, it may be that behaviors earlier in life mediate hormone levels and subsequent disease risk.

title: Biomarkers of fatty acid exposure and breast cancer risk.
abstract: Study of the effects of most individual biologically active dietary fatty acids on human disease requires the use of biomarkers of long-term intake in well-designed epidemiologic studies. Several small studies of tissue taken from women undergoing surgery for breast abnormalities have compared fatty acid profiles of women with ascertained metastatic breast cancer with those with other abnormalities. These studies, although often flawed in design and generally of inadequate statistical power to determine significant differences, provide some evidence. Human studies are generally consistent with animal models suggesting a protective effect of n-3 fatty acids, a detrimental effect of high n-6 fatty acids, and the possible importance of the ratio of these two classes of dietary fatty acids on both breast cancer incidence and recurrence. High intakes of monounsaturated fatty acid were also often negatively associated with breast cancer. The effects of trans fatty acids have rarely been studied, but there are some indications that they may enhance risk. In general, the study of individual fatty acids is in its infancy. Larger well-designed studies with diverse population and modern analyses of individual fatty acids are needed.

title: Classification of endometrial carcinoma: more than two types.
abstract: Endometrial cancer is the most common gynaecological malignancy in Europe and North America. Traditional classification of endometrial carcinoma is based either on clinical and endocrine features (eg, types I and II) or on histopathological characteristics (eg, endometrioid, serous, or clear-cell adenocarcinoma). Subtypes defined by the different classification systems correlate to some extent, but there is substantial heterogeneity in biological, pathological, and molecular features within tumour types from both classification systems. In this Review we provide an overview of traditional and newer genomic classifications of endometrial cancer. We discuss how a classification system that incorporates genomic and histopathological features to define biologically and clinically relevant subsets of the disease would be useful. Such integrated classification might facilitate development of treatments tailored to specific disease subgroups and could potentially enable delivery of precision medicine to patients with endometrial cancer.