Associations between diet and cardiometabolic risk among Yup'ik Alaska Native people using food frequency questionnaire dietary patterns.

BACKGROUND AND AIMS: In previous analyses, we identified three dietary patterns from food frequency questionnaire data among a sample of Yup'ik Alaska Native people living in Southwest Alaska: a "subsistence foods" dietary pattern and two market-based dietary patterns "processed foods" and "fruits and vegetables". In this analysis, we aimed to characterize the association between the dietary patterns and cardiometabolic (CM) risk factors (lipids, blood pressure, glucose, adiposity). METHODS AND RESULTS: We used multilevel linear regression to estimate the mean of each CM risk factor, comparing participants in the 4th to the 1st quartile of each dietary pattern (n = 637). Models were adjusted for age, sex, past smoking, current smoking, and physical activity. Mean log triglyceride levels were significantly higher among participants in the 4th compared to the 1st quartile of the processed foods dietary pattern (ß = 0.11). Mean HbA1c percent was significantly lower (ß = -0.08) and mean diastolic blood pressure (DBP) mm Hg was significantly higher (ß = 2.87) among participants in the 4th compared to the 1st quartile of the fruits and vegetables dietary pattern. Finally, mean log triglyceride levels and mean DBP mm Hg were significantly lower among participants in the 4th compared to the 1st quartile of the subsistence foods dietary pattern (ß = -0.10 and ß = -3.99 respectively). CONCLUSIONS: We found increased CM risk, as reflected by increased triglycerides, associated with eating a greater frequency of processed foods, and reduced CM risk, as reflected by lower triglycerides and DBP, associated with eating a greater frequency of subsistence foods.

Which measure of adolescent psychiatric disorder--diagnosis, number of symptoms, or adaptive functioning--best predicts adverse young adult outcomes?

OBJECTIVE: To test the ability of psychiatric diagnosis, symptom count, and adaptive functioning in adolescence to predict failure to complete secondary school and criminal involvement in young adulthood. DESIGN: Community-based cohort study. SETTING: Two counties in upstate New York, USA. PARTICIPANTS: 181 adolescents interviewed in 1983 and 1985-86 who were randomly selected in 1975 from a probability area sampling of representative families with 1-10 year old children. MAIN RESULTS: Compared with adolescents without psychiatric disorders, adolescents with depressive, anxiety, disruptive, and substance abuse disorders were 2.86-9.21 times more likely to fail to complete secondary school. Compared with adolescents without disruptive disorders, adolescents with disruptive disorders were 4.04 (1.96-8.32) times more likely to get in trouble with police during young adulthood. The positive predictive value of each measure of adolescent psychiatric disorder for school non-completion was higher in the lowest SES stratum and for young adult criminal involvement was higher for boys. Combining knowledge of symptom counts, age, gender, and social class in a logistic regression model yielded 89% sensitivity and 87% specificity for predicting future school non-completion at the p >or= 0.13 cut off. The optimal cut off value in a model incorporating knowledge of disruptive symptoms and demographic characteristics yielded 75% sensitivity and 76% specificity for predicting future criminal involvement. CONCLUSIONS: Screening children and adolescents for psychiatric disorders can identify those at high risk of adverse young adult outcomes. Future school and community adjustment can be predicted as easily and accurately on the basis of a simple count of psychiatric symptoms as by applying more complex diagnostic algorithms. Screening youth for psychiatric symptoms in neighbourhood, school, or primary care settings is a logical first step for early intervention to promote increased school completion and decreased criminal activity in young adulthood.

Recreational physical activity and endometrial cancer risk.

To investigate the association between recreational physical activity and endometrial cancer risk, a population-based case-control study was conducted in Washington State. The study included 822 incident cases of endometrial cancer diagnosed between 1985 and 1991 and 1,111 randomly selected population-based controls. Detailed information on recreational physical activities as well as other endometrial cancer risk factors was obtained in structured, in-person interviews. Unconditional logistic regression, adjusted for age, county, energy intake, unopposed estrogen use, income, and, in separate models, body mass index (kg/m(2)), was used to estimate the odds ratios and their 95% confidence intervals, relating endometrial cancer to each level of physical activity. A greater proportion of controls (49.3%) than cases (40.5%) reported doing regular exercise (compared with no exercise: adjusted odds ratio = 0.62, 95% confidence interval: 0.51, 0.76) in the 2-year period prior to diagnosis date. There was little evidence of a trend of decreasing risk with increasing duration or intensity of recreational physical activities. These results provide support for an association between the lack of recent recreational physical activity and endometrial cancer risk. However, the absence of a difference by duration or intensity levels and the inconsistent results from other studies suggest caution before interpreting this association as causal.

Risk factors for synchronous primary endometrial and ovarian cancers.

PURPOSE: The incidence of synchronous primary endometrial and ovarian cancer is 2- to 10-fold higher than that expected based on the incidence of each cancer alone. We sought to evaluate reasons for this in a case-control study. METHODS: We combined data on a maternal history of cancer and reproductive and menstrual factors from 56 women with synchronous multiple primary disease who had participated in three population-based studies of gynecologic cancer. For comparison, we analyzed the same information from 280 women with endometrial cancer alone, 280 with ovarian cancer alone, and 280 without a history of either cancer. RESULTS: The reduced risk of multiple primary disease associated with high parity (2 or more births vs 0: OR = 0.37, 95% Cl, 0.19-76) and long-term use of oral contraceptives (12 or more months vs none: OR = 0.60, 95% Cl, 0.24-1.5) tended to be more pronounced than that associated with endometrial cancer alone or with ovarian cancer alone. CONCLUSIONS: Though limited by relatively small numbers, our results suggest that the presence of some common etiologies is a basis for the unusually high co-occurrence of endometrial and ovarian cancers.

Folic acid: are current fortification levels adequate?

OBJECTIVE: Beginning on January 1, 1998, all cereal and grain products in the United States were fortified with folic acid to reduce the occurrence of the very common congenital malformations known as neural-tube defects. Three years have passed since the fortification program began, and it is time to evaluate whether the current fortification levels have met their intended objective. METHODS: We offer an overview of folate and its potential role in the etiology of neural-tube defects, review some of the highlights of the deliberations that led to the decision by the Food and Drug Administration to fortify the food supply, and offer a perspective on how to measure whether current fortification levels are adequate. RESULTS: There is no national system in the United States that monitors neural-tube and other birth defects over time, and no postmarketing surveillance was mandated to monitor the safety of the fortification program. Therefore, we must evaluate the program in other ways. Blood biomarkers of folate status such as the levels of folate in red blood cells and homocysteine in plasma provided the best evidence of the effectiveness of the folic-acid-fortification program because of their relatively high sensitivities in relation to their specificities as markers of folate status. In addition, these biomarkers might provide information about the risks of other diseases related to folate status such as vascular disease. CONCLUSION: Federal agencies should coordinate efforts to gather and evaluate markers of folate status at the population level. These measures can be used to evaluate the safety and efficacy of folic-acid fortification and whether changes are warranted in fortification levels.

Effect of health lifestyle pattern on dietary change.

PURPOSE: To examine the effect of lifestyle on the effectiveness of a low-intensity dietary intervention. DESIGN: A secondary data analysis was performed using data from the Eating Patterns Study, a randomized controlled trial that found that self-help materials with physician advice was effective in changing dietary intake and behavior. SETTING: Primary care clinics in a large health maintenance organization. SUBJECTS: A total of 2111 patients with a routine scheduled appointment with their primary care physicians. MEASURES: Participants were grouped into one of six health lifestyle patterns based on similarities in baseline measures of alcohol intake, smoking, diet quality, and exercise. Within each lifestyle pattern, changes from baseline in usual fat and fiber intake (based on a food frequency) and a fat and fiber behavior score were compared at 3 months and 12 months for intervention vs. control participants. INTERVENTION: Self-help materials delivered by a physician with advice to change diet. RESULTS: Intervention participants in the fitness lifestyle group made the largest changes relative to controls for each dietary outcome at 3 and 12 months. For intervention participants defined by their alcohol intake or current smoking, either no changes in diet were observed compared with controls, or early changes were not sustained over time. Intervention-control comparisons within the remaining lifestyle patterns showed smaller dietary changes compared with the fitness lifestyle. This finding was similar to previously published results. CONCLUSIONS: This randomized controlled trial had limited power to detect subgroup differences; however, these results suggest that lifestyle patterns may be useful in the development of effective, targeted interventions to change behavior.

The association of dietary fat and plant foods with endometrial cancer (United States).

OBJECTIVES: To examine the associations of dietary fat and selected plant foods with endometrial cancer in a population-based case-control study. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Indirect calorimetry protocol development for measuring resting metabolic rate as a component of total energy expenditure in free-living postmenopausal women.

An objective measure of energy intake is needed in epidemiologic studies to evaluate random and systematic error associated with dietary self-report tools. Total energy expenditure in weight-stable humans is accepted as a measure of energy intake, but doubly labeled water remains cost prohibitive for large studies. Our purpose was to develop a practical indirect calorimetry (IC) protocol for estimating resting metabolic rate (RMR) in free-living, postmenopausal women. We conducted duplicate IC measures 1 wk apart using a canopy system on 102 women ages 50-79 y from the Seattle area. We compared RMR for 0-5, 5-10, 5-15, 5-20, 5-25, 5-30, and 0- to 30-min IC segments and segments meeting stability criteria. The mean RMR for the first 5 min was significantly higher than other time segments (P = 0.001). Correlation coefficients between duplicate measures were high (r = 0.90). Use of defined stability criteria produced RMR measures that were 10-30 kcal (42-126 kJ) higher than the 5- to 10-min RMR measures and 40-60% of subjects did not achieve these stability criteria. For protocols including IC to assess RMR as a component of total energy expenditure in free-living, postmenopausal women, a single 10-min canopy study, excluding the first 5 min of data, produces reliable results with minimal subject burden.

Differential effects of phosphatidylinositol-3/Akt-kinase inhibition on apoptotic sensitization to cytokines in LNCaP and PCc-3 prostate cancer cells.

Alterations in phosphatidylinositol 3'-kinase (PI3'-kinase) and Akt activation frequently occur in prostate cancer and may disrupt apoptotic induction by such cytokines as tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL). To examine the role of PI3' phosphorylation in the cellular response to cytokines, two prostate cancer cell lines with constitutively activated PI3'-kinase cascades (LNCaP and PC-3) were examined for direct sensitivity to cytokines. TNF or TRAIL alone failed to activate apoptosis in either LNCaP or PC-3 cells, and drug-mediated inhibition of the PI3k/Akt cascade caused only minimal activation of apoptosis in either cell line. Suppression of PI3'-kinase/Akt signaling markedly enhanced the apoptotic activity of both TNF and TRAIL in LNCaP cells but not in PC-3 cells. Adenovirus-mediated PTEN/MMAC1 expression in LNCaP cells reduced Akt activation, activated apoptosis, and sensitized cells to TNF but not to TRAIL. Together, these results suggest that PI3'-kinase signaling inhibits both TNF-mediated and TRAIL-mediated apoptosis but may represent one of several apoptotic resistance mechanisms that inhibit cytokine-mediated killing of prostate cancer cells.

Seattle 5 a Day worksite program to increase fruit and vegetable consumption.

BACKGROUND: 5 a Day for Better Health is a simple message encouraging people to eat more fruits and vegetables. The Seattle 5 a Day worksite investigators designed and evaluated an intervention, organized on stages of behavioral change, to increase worksitewide fruit and vegetable consumption. METHODS: We recruited 28 worksites with cafeterias and randomized 14 to intervention and 14 to control. The intervention addressed both changes in the work environment and individual level behavior change. In each worksite, an employee advisory board, with study interventionist assistance, implemented the program. By surveying cross-sectional samples of 125 employees per worksite, we compared worksite mean fruit and vegetable consumption at 2-year follow-up with that at baseline. Unobtrusive site-level indicators including plate observation and cafeteria checklist were also used. RESULTS: The difference at 2 years was 0.5 for the intervention worksites and 0.2 for the control worksites, with an intervention effect of 0.3 daily serving (P < 0.05). Other measures of fruit and vegetable consumption, including unobtrusive indicators, supported the effectiveness of the intervention. CONCLUSIONS: This simple 5 a Day intervention is feasible and acceptable for use in worksites with cafeterias. There was a significant differential increase in fruit and vegetable consumption in the intervention worksites. This kind of worksite intervention can achieve important health benefits on a population basis, because of its potential to reach large numbers of people.

Continuous combined hormone replacement therapy and risk of endometrial cancer.

OBJECTIVE: Postmenopausal women who receive sequential hormone replacement therapy with estrogen combined with progestogen for 10 to 24 d/mo for a prolonged period may have an elevated endometrial cancer risk relative to those who have never received hormone replacement therapy. We investigated whether daily use of estrogen and progestogen (continuous combined hormone replacement therapy) could diminish any excess endometrial cancer risk. STUDY DESIGN: A population-based study in Washington State obtained interview data from 969 women aged 45 to 74 years with endometrial cancer diagnosed during 1985 through 1991 or 1994 through 1995 and from 1325 age-matched control subjects selected primarily by random digit dialing. Women who had received only continuous combined hormone replacement therapy were compared with women who had only received another hormone replacement therapy regimen or who had never received hormone replacement therapy. RESULTS: The risk of endometrial cancer among users of continuous combined hormone replacement therapy (n = 9 case patients, n = 33 control subjects) relative to women who had never received hormone replacement therapy was 0.6 (95% confidence interval, 0.3-1.3); the risk relative to women who received hormone replacement that included progestogen for 10 to 24 d/mo was 0.4 (95% confidence interval, 0.2-1.1). Most continuous combined hormone replacement therapy use was short-term (<72 months) or recent (in the previous 24 months). CONCLUSION: Women who had received continuous combined hormone replacement therapy for several years did not appear to be at any increased risk for endometrial cancer relative to women who had never received hormone replacement therapy and may in fact be at decreased risk for endometrial cancer.

Community-based study of the transition to adulthood for adolescents with psychiatric disorder.

This longitudinal study examines the transition to adulthood in a randomly sampled, community-based cohort of adolescents. The study compares young adult outcomes of 33 adolescents with and 148 adolescents without psychiatric disorder. After adjustment for differences in age, gender, and social class, adolescents with psychiatric disorder were 13.74 times less likely to complete secondary school (95% confidence interval (CI): 4.17, 45.17), 4.07 times less likely to be employed or in college or trade school (95% CI: 1.4, 12.3), 3.13 times more likely to be involved in criminal activity (95% CI: 1.11, 8.87), and 6.46 times more likely to have gotten pregnant themselves or to have gotten someone else pregnant (95% CI: 1.75, 23.87). While adolescents with psychiatric disorder in this community-based study had outcomes that were somewhat more favorable than those of adolescents with psychiatric disorder in prior treatment-based studies, they nonetheless are at high risk of failing to meet young adult role expectations.

The controversy over homocysteine and cardiovascular risk.

Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebo-controlled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.

Increased risk of hip fracture among patients with end-stage renal disease.

BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for bone loss, the risk of hip fracture in this population is not known. We compared the risk of hip fracture among dialysis patients with the general population. METHODS: We used data from the United States Renal Data System (USRDS) to identify all new Caucasian dialysis patients who began dialysis between January 1, 1989, and December 31, 1996. All hip fractures occurring during this time period were ascertained. The observed number of hip fractures was compared with the expected number based on the experience of residents of Olmstead County (MN, USA). Standardized incidence ratios were calculated as the ratio between observed and expected. The risk attributable to ESRD was calculated as the difference between the observed and expected rate of hip fracture per 1000 person-years. RESULTS: The number of dialysis patients was 326,464 (55.9% male and 44.1% female). There were 6542 hip fractures observed during the follow-up period of 643, 831 patient years. The overall incidence of hip fracture was 7.45 per 1000 person years for males and 13.63 per 1000 person years for females. The overall relative risk for hip fracture was 4.44 (95% CI, 4.16 to 4.75) for male dialysis patients and 4.40 (95% CI, 4.17 to 4.64) for female dialysis patients compared with people of the same sex in the general population. While the age-specific relative risk of hip fracture was highest in the youngest age groups, the added risks of fracture associated with dialysis rose steadily with increasing age. The relative risk of hip fracture increased as time since first dialysis increased. CONCLUSIONS: The overall risk of hip fracture among Caucasian patients with ESRD is considerably higher than in the general population, independent of age and gender.

Lack of association between the C677T MTHFR polymorphism and colorectal hyperplastic polyps.

Colorectal hyperplastic polyps are benign lesions that share many risk factors with colorectal adenomas and cancers. Low folate intakes are associated with an increased risk of colon cancer. The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) may be linked to DNA methylation and nucleotide synthesis and thus play a role in the etiology of colorectal neoplasia. We investigated an association between the common MTHFR polymorphism (C677T) and colorectal hyperplastic polyps within the Minnesota Cancer Prevention Research Unit case-control study. Cases (n = 200) were diagnosed with colonoscopically confirmed hyperplastic polyps; controls (n = 645) were derived from the same gastroenterology practice and were polyp-free at colonoscopy. Dietary intakes were estimated from a self-administered food-frequency questionnaire prior to colonoscopy. Multivariate adjusted odds ratios (ORs) and 95% confidence intervals for MTHFR status were 0.8 (0.6-1.2; CT versus CC wild-type) and 0.9 (0.5-1.6; TT versus CC). In subgroup analyses stratified on dietary intakes of folate, vitamin B12, vitamin B6, or methionine, those with the TT genotype and either low intakes of folate or vitamin B6 were at increased risk relative to those with normal or high vitamin intake. However, most 95% confidence intervals included 1.0, and no consistent trends were observed. In contrast to our findings on colorectal adenomas, increasing alcohol consumption was associated with an elevated risk of colorectal hyperplastic polyps, regardless of genotype. The MTHFR (C677T) variant genotype does not appear to be related to risk of colorectal hyperplastic polyps, and there is no convincing evidence that MTHFR shows a different relation to risk, dependent on dietary intakes of nutrients related to its pathway.

Seattle 5-a-Day Work-Site Project: process evaluation.

The Seattle 5-a-Day Work-Site Project developed a community-based intervention to increase fruit and vegetable intake, using both environmental (including cafeteria and work-site-wide events) and individual strategies. The Employee Advisory Board developed its own protocol from a common skeleton and a minimum set of activities. Small work sites and work sites with fewer female employees delivered more displays, posters, and table tents per employee (p < .01 and p < .05, respectively). Dose was neither related to use of the intervention nor to change in fruit and vegetable intake. Use of informational materials increased fruit and vegetable intake in the cohort of employees with both baseline and follow-up data (p = .05). The intervention was associated both with increased employee use of the intervention (activities and materials) and with increased intake of fruit and vegetables. Work sites with medium average baseline intake were the most responsive. These findings can guide the development of more efficient community-based dietary interventions.

Implementing a dietary intervention in primary care practice: a process evaluation.

OBJECTIVES: Physicians acknowledge the need to advise their patients about dietary habits, but they may not have the training or tools to do this efficiently. In the context of a randomized trial, we investigated the feasibility of enlisting physicians to implement a dietary intervention in the primary care setting. METHODS: Physicians from 14 primary care practices were assigned via randomization to introduce a self-help booklet to promote dietary change at routine appointments. Delivery of the booklet was recorded by these intervention physicians at the clinic appointment; intervention participants were asked 3 months later in a telephone interview about whether they received and used the booklet. RESULTS: According to physician documentation, 95% of intervention participants who kept an appointment (n = 935) received the booklet; among participants completing a 3-month interview (n = 890), 96% reported the same. However, only about 50% of participants reported receiving the booklet from their physician; the remainder received the booklet from other clinic staff. Overall, 93% reported reading at least part of the booklet. Use of the booklet varied little whether it was delivered by a physician or staff person, but it was more likely to be read as time spent discussing the booklet increased. CONCLUSIONS: Physician cooperation and evidence of intervention effectiveness support the use of primary care for the delivery of interventions to change diet; training the entire health team and repeating dietary advice at subsequent visits may improve the success of such interventions.

Apolipoprotein E genotype and the risk of gallbladder disease in pregnancy.

The E4 allele of apolipoprotein E (apoE4) has previously been associated with symptomatic gallstone disease. The aim of this study was to determine if apoE4 is associated with the development of gallbladder sludge and/or stones during pregnancy. We conducted a nested case-control study based on an ongoing cohort study of gallbladder disease in pregnancy. Women in this study receive gallbladder ultrasounds in each trimester of pregnancy. Cases (n = 52) were defined as women with incident gallbladder sludge or stones diagnosed at the third trimester ultrasound. Controls (n = 104) were defined as women without gallbladder sludge or stones on any of 3 study ultrasounds. ApoE genotyping was performed from stored white blood cell pellets. Data were analyzed by stratified analysis and multivariate logistic regression. Cases and controls were similar in baseline characteristics. Forty-two women had sludge, 6 had gallstones, and 4 had both sludge and stones. After adjusting for risk factors such as age, parity, and body mass index, the odds ratio (OR) for the association between heterozygosity or homozygosity for the apoE4 allele and incident gallbladder sludge or stones was 0.91 (95% confidence interval [CI], 0.41-2.02). Further adjustment for family medical history and serum lipid levels did not substantially change these results (OR, 0.73; 95% CI, 0.29-1.82). In conclusion, apoE4 appears to have little or no overall association with the development of new gallbladder sludge or stones in pregnancy. However, an effect could not be ruled out in certain subgroups, such as blacks or women who are homozygous for apoE4.

The additional risk of endometrial cancer associated with unopposed estrogen use in women with other risk factors.

We analyzed data from a population-based case-control study of endometrial cancer. Our goal was to identify a subgroup of women in whom the additional cancer risk associated with unopposed estrogen use was sufficiently small so as to not be a deterrent to taking a hormone preparation of this type. Researchers interviewed women with endometrial cancer (N = 553) and controls (N = 752) regarding hormone use. The additional risk of endometrial cancer associated with unopposed estrogen use did not vary substantially in the presence or absence of hypertension, parity, oral contraceptive use, or smoking. The results suggest that, although heavier women may experience a greater risk of endometrial cancer associated with unopposed estrogen use (8.2 per 1,000 per year) than lighter women (4.2 per 1,000 per year), long-term users in the latter group nonetheless face a substantial absolute increase in risk. We conclude that subdividing women on the basis of the presence or absence of other known risk factors for endometrial cancer fails to delineate a subgroup that is exempt from the increased risk of this cancer associated with use of unopposed estrogens. 83.6% of estrogen users reported taking conjugated estrogens.