Physical Activity and Risk of Endometrial Cancer: A Report from the Shanghai Endometrial Cancer Study

We evaluated the type and amount of physical activity associated with risk of endometrial cancer. In this population-based case-control study, in-person interviews were completed among 832 incident endometrial cancer cases and 846 age-matched controls. Physical activity from exercise, household activities, and transportation was assessed in adolescence and adulthood, as was lifetime occupational activity. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence limits (95% CL). Women reporting exercise participation in both adolescence and adulthood were at nearly a 40% reduced risk (OR, 0.63; 95% CL, 0.42-0.95), compared with women reporting no exercise in either life period. Postmenopausal women who initiated exercise in adulthood were also at reduced risk (OR, 0.76; 95% CL, 0.56-1.02). Reductions in risk were also observed for common lifestyle activities, including household activity (both life periods) and walking for transportation (adulthood). Examination of the independent and combined effect of exercise and lifestyle activities revealed that women with less active lifestyles but who reported exercise were at 35% reduced risk (OR, 0.65; 95% CL, 0.41-1.02), whereas nonexercisers with more active lifestyles were at 40% to 45% reduced risk. These findings suggest that both lifestyle activities of lower intensity (e.g., walking and doing household chores) and intentional exercise can reduce endometrial cancer risk.

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title: Selected physical activities and the risk of endometrial cancer.
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title: Past and present physical activity and endometrial cancer risk.
abstract: We examined the relation between physical activity and endometrial cancer using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. Estimates of recreational (i.e. active sport, walks and hikes) and nonrecreational activity (i.e. house cleaning, climbing stairs and walking or standing on the job) were obtained using interview information. After adjustment for age, study area, education, parity, years of use of oral contraceptives, years of use of menopausal oestrogens and cigarette smoking, recent recreational inactivity was associated with increased risk (RR = 1.9 for lowest vs highest tertile). Similarly, recent nonrecreational inactivity was associated with increased risk (RR = 2.2 for lowest vs highest tertile). Further adjustment for body mass and nonrecreational activity attenuated the association between risk and recent recreational inactivity (RR = 1.2; 95% CL = 0.7-2.0) but adjustment for body mass and recreational activity did not alter the association between risk and recent nonrecreational inactivity (RR = 2.0; 95% CL = 1.2-3.1). To evaluate the relation between risk and sustained inactivity, we simultaneously examined activity levels at three periods (RR i.e. age 20-29, age 30-39 and recently) in women age 50 and older. After adjustment for potential confounders and body mass, risk was elevated among women who were always recreationally inactive (RR = 1.5 for always active vs always inactive) and among women who were always nonrecreationally inactive (RR = 1.6 for always active vs always inactive). This study suggests that physically inactive women may be at increased risk of endometrial cancer because they are more likely to be overweight or obese. Our data also suggest that inactivity per se may be associated with an increased risk of endometrial cancer. However, we cannot rule out the possibility that our results, particularly those for nonrecreational activity, reflect unmeasured confounding factors. Future studies should attempt to obtain more detailed assessments of physical activity, including the intensity with which an individual engaged in an activity and the actual time involved in exertion.

title: Recreational physical activity and endometrial cancer risk.
abstract: 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.

title: Effect of adiposity and fat distribution on endometrial cancer risk in Shanghai women.
abstract: The authors conducted a population-based case-control study of 832 endometrial cancer cases and 846 frequency-matched controls in Shanghai, China (1997-2001), to examine the association of overall adiposity and body fat distribution with disease risk. Overall adiposity was estimated using weight and body mass index (BMI); upper body fat distribution was evaluated using waist circumference and waist:hip ratio. Overall and upper-body obesity were both associated with an elevated risk of endometrial cancer. Adjusted odds ratios and 95% confidence intervals for highest-versus-lowest quartile comparisons were 2.6 (95% confidence interval (CI): 2.0, 3.5) for weight, 2.9 (95% CI: 2.2, 3.9) for BMI, 4.7 (95% CI: 3.4, 6.4) for waist circumference, and 3.5 (95% CI: 2.6, 4.8) for waist:hip ratio. The positive associations with weight and BMI vanished after results were controlled for waist circumference, while associations with waist circumference and waist:hip ratio persisted after adjustment for BMI. The positive association with upper-body obesity was more pronounced among younger women, women who had never used oral contraceptives, and women with a history of diabetes mellitus (p for multiplicative interaction < 0.05). Upper-body obesity was related to increased risk among women with low BMI. These results suggest that obesity, particularly upper-body fat deposition, is associated with an increased risk of endometrial cancer.

title: Compendium of physical activities: an update of activity codes and MET intensities.
abstract: We provide an updated version of the Compendium of Physical Activities, a coding scheme that classifies specific physical activity (PA) by rate of energy expenditure. It was developed to enhance the comparability of results across studies using self-reports of PA. The Compendium coding scheme links a five-digit code that describes physical activities by major headings (e.g., occupation, transportation, etc.) and specific activities within each major heading with its intensity, defined as the ratio of work metabolic rate to a standard resting metabolic rate (MET). Energy expenditure in MET-minutes, MET-hours, kcal, or kcal per kilogram body weight can be estimated for specific activities by type or MET intensity. Additions to the Compendium were obtained from studies describing daily PA patterns of adults and studies measuring the energy cost of specific physical activities in field settings. The updated version includes two new major headings of volunteer and religious activities, extends the number of specific activities from 477 to 605, and provides updated MET intensity levels for selected activities.

title: Reproducibility and validity of the Shanghai Women's Health Study physical activity questionnaire.
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title: Case–control study of diabetes, obesity, physical activity and risk of endometrial cancer among Mexican women
abstract: Obesity, hypertension and diabetes are closely associated with endometrial cancer (EC). This study evaluates the relationship between diabetes and risk of EC on the basis of obesity.
 A case–control study was carried out in Mexico City from 1995 to 1997. Eighty-five histologically confirmed cases were compared with 668 population-based controls obtained through frequency matching. Diabetes status, weight, height and other factors were determined through personal interviews among both cases and controls.
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title: Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.
abstract: Endometrial cancer is a disease of the affluent, developed world, where epidemiological studies have shown that > or =40% of its incidence can be attributed to excess body weight. An additional proportion may be because of lack of physical activity. Alterations in endogenous hormone metabolism may provide the main links between endometrial cancer risk, and excess body weight and physical inactivity. Epidemiological studies have shown increased endometrial cancer risks among pre- and postmenopausal women who have elevated plasma androstenedione and testosterone, and among postmenopausal women who have increased levels of estrone and estradiol. Furthermore, there is evidence that chronic hyperinsulinemia is a risk factor. These relationships can all be interpreted in the light of the "unopposed estrogen" hypothesis, which proposes that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In our overall synthesis, we conclude that development of ovarian hyperandrogenism may be a central mechanism relating nutritional lifestyle factors to endometrial cancer risk. In premenopausal women, ovarian hyperandrogenism likely increases risk by inducing chronic anovulation and progesterone deficiency. After the menopause, when progesterone synthesis has ceased altogether, excess weight may continue increasing risk through elevated plasma levels of androgen precursors, increasing estrogen levels through the aromatization of the androgens in adipose tissue. The ovarian androgen excess may be because of an interaction between obesity-related, chronic hyperinsulinemia with genetic factors predisposing to the development of ovarian hyperandrogenism.

title: Moderate-intensity physical activity and fasting insulin levels in women: the Cross-Cultural Activity Participation Study.
abstract: The purpose of this study was to determine the association between moderate-intensity physical activity (PA) and fasting insulin levels among African-American (n = 47), Native American (n = 46), and Caucasian women (n = 49), aged 40-83 years, enrolled in the Cross-Cultural Activity Participation Study. Associations by race/ethnicity, levels of central obesity, and cardiorespiratory fitness were also examined.



Physical activity scores were obtained from detailed PA records that included all PA performed during two consecutive 4-day periods scheduled 1 month apart. Using MET intensity (the associated metabolic rate for a specific activity divided by a standard resting metabolic rate), PA was expressed as MET-min (the product of the minutes for each activity times the MET intensity level) per day of energy expended in moderate (3-6 METs) and moderate/vigorous (> or = 3 METs) PA. Fasting insulin levels were determined by radioimmunoassay. Data were analyzed by multiple linear regression analysis.



After adjusting for race/ethnicity, age, educational attainment, and site, an increase of 30 min of moderate-intensity PA was associated with a 6.6% lower fasting insulin level (P < 0.05). The association was similar among races/ethnicities, centrally lean and centrally obese women, and women with low and high cardiorespiratory fitness levels.



These findings lend support to the 1995 Centers for Disease Control and Prevention and American College of Sports Medicine recommendations for an accumulation of 30 min/day in moderate-intensity PA. They also contribute to the growing literature suggesting that moderate amounts of PA have a significant role in reducing the burden of hyperinsulinemia and diabetes among ethnic populations at highest risk for these conditions.

title: Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study.
abstract: Exercise training is associated with improved insulin sensitivity (SI), but the potential impact of habitual, nonvigorous activity is uncertain.



To determine whether habitual, nonvigorous physical activity, as well as vigorous and overall activity, is associated with better SI.



A multicultural epidemiologic study.



The Insulin Resistance Atherosclerosis Study, conducted in Oakland, Calif; Los Angeles, Calif; the San Luis Valley, Colo; and San Antonio, Tex.



A total of 1467 men and women of African American, Hispanic, and non-Hispanic white ethnicity, aged 40 to 69 years, with glucose tolerance ranging from normal to mild non-insulin-dependent diabetes mellitus.



Insulin sensitivity as measured by an intravenous glucose tolerance test.



The mean SI for individuals who participated in vigorous activity 5 or more times per week was 1.59 min(-1) x microU(-1) x mL(-1) x 10(-4) (95% confidence interval [CI], 1.39-1.79) compared with 0.90 (95% CI, 0.83-0.97) for those who rarely or never participated in vigorous activity, after adjusting for potential confounders (P<.001). When habitual physical activity (estimated energy expenditure [EEE]) was assessed by 1-year recall of activities, the correlation coefficient between SI and total EEE was 0.14 (P<.001). After adjustment for confounders, vigorous and nonvigorous levels of EEE (metabolic equivalent levels > or = 6.0 and <6.0, respectively) were each positively and independently associated with SI (P< or =.01 for each). The association was attenuated after adjustment for the potential mediators, body mass index (a measure of weight in kilograms divided by the square of the height in meters), and waist-to-hip ratio. Results were similar for subgroups of sex, ethnicity, and diabetes.



Increased participation in nonvigorous as well as overall and vigorous physical activity was associated with significantly higher SI. These findings lend further support to current public health recommendations for increased moderate-intensity physical activity on most days.

title: Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial.
abstract: Elevated circulating estrogens and a sedentary lifestyle increase risk for breast cancer. The effect of exercise on circulating estrogens in sedentary postmenopausal women is unknown. The objective of this study was to examine the effects of a 12-month moderate-intensity exercise intervention on serum estrogens. We randomly assigned 173 sedentary, overweight (body mass index > 24.0 kg/m(2), body fat > 33%), postmenopausal women, ages 50-75 years, not using hormone therapy, living in the Seattle, Washington, area for the next year, and willing to be randomly assigned to an exercise intervention or stretching control group. The exercise intervention included facility and home-based exercise (45 min, 5 days/week moderate intensity sports/recreational exercise). A total of 170 (98.3%) women completed the study with exercisers averaging 171 min/week of exercise. After 3 months, exercisers experienced declines in estrone, estradiol, and free estradiol of 3.8, 7.7, and 8.2%, respectively, versus no change or increased concentrations in controls (P = 0.03, 0.07, and 0.02, respectively). At 12 months, the direction of effect remained the same, although the differences were no longer statistically significant. The effect was limited to women who lost body fat: women whose percentage of body fat [by dual energy x-ray absortiometry (DEXA)] decreased by >/==" BORDER="0">2% had statistically significant (comparing exercisers versus controls) decreases at 12 months of 11.9, 13.7, and 16.7% for serum estrone, estradiol, and free estradiol, respectively. We concluded that a 12-month moderate-intensity exercise intervention in postmenopausal women resulted in significant decreases in serum estrogens. The association between increased physical activity and reduced risk for postmenopausal breast cancer may be partly explained by effects on serum estrogens.

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: Physical activity and risk of endometrial cancer in a prospective cohort study (United States)
abstract: To examine the physical activity and endometrial cancer relationship in a prospective study of US women enrolled in the Breast Cancer Detection Demonstration Project (BCDDP) Follow-up Study.  We assessed past-year physical activity of all types in 23,369 women who returned the baseline questionnaire (1987–1989) and had no prior hysterectomy and/or endometrial cancer. Cox proportional hazards models were used to estimate age, education, and parity-adjusted rate ratios (RR) and 95% confidence intervals (CI) for the 253 confirmed endometrial cancer cases identified during an average 8.2 years of follow-up (ending 1995–1998).  There were no dose–response relationships with either total or vigorous physical activity; however, compared to the lowest total activity quartile, the higher four quartiles had a non-significantly lower risk (RR = 0.8, CI = 0.6–1.0). The association with moderate activity varied with follow-up time: RRs (CI) for a 1 h increase in daily moderate activity within 2-year intervals of follow-up (≤2, 2.1–4.9, 5.0–8.0, >8 years) were 1.1 (1.0, 1.2), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), 1.0 (0.9, 1.1), and 0.8 (0.7, 1.0), respectively.  These data suggest that recent physical activity is not strongly related to the risk of endometrial cancer, and that prolonged exposure and longer follow-up may be necessary.

title: American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer with Healthy Food Choices and Physical Activity
abstract: The American Cancer Society (ACS) has set aggressive challenge goals for the nation to decrease cancer incidence and mortality—and to improve the quality of life of cancer survivors—by the year 2015.

title: Physical activity and postmenopausal endometrial cancer risk (Sweden)
abstract: To examine the hypothesis that sedentary women have an increased risk of endometrial cancer compared to physically active women.
This is a population-based case–control study in the entire Swedish female population aged 50–74 years in 1994–1995. We obtained self-reported information on leisure-time physical activity during childhood, at ages 18–30, and recently from 709 incident case women with endometrial cancer and 3368 population controls. Occupational physical activity was estimated through record linkage to the Swedish census data from 1960, 1970, 1980, and 1990. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for different activity levels by multivariate logistic regression, taking into account potential confounders.
Comparing lowest to highest (reference) levels of physical exercise, we observed statistically significant associations with risk of endometrial cancer for leisure-time activity at age 18–30 years (multivariate OR = 1.4; 95% CI = 1.0–1.8; p for trend 0.01) and in recent years (multivariate OR=1.3; 95% CI = 1.0–1.7; p for trend 0.01). We found similar associations comparing lowest to highest (reference) levels of occupational activity assessed at the censuses in 1980 (multivariate OR = 1.4; 95% CI = 1.0–1.9; p for trend 0.03) and 1990 (multivariate OR = 1.3; 95% CI = 0.9–1.9, p for trend 0.05), but a less consistent association with censuses in 1960 and 1970. The increased risk associated with low level of occupational physical activity was confined to women who were not obese and to women who were smokers.
Our data, in conjunction with past epidemiological studies, indicate that both occupational and leisure-time physical activity may reduce the risk for postmenopausal endometrial cancer.

title: Lifetime physical activity and breast cancer risk in the Shanghai Breast Cancer Study
abstract: Overall physical activity in adolescence and adulthood, and changes in activity over the lifespan were analysed by in-person interviews among 1459 women newly diagnosed with breast cancer and 1556 age-matched controls in urban Shanghai. Physical activity from exercise and sports, household, and transportation (walking and cycling) was assessed in adolescence (13–19 y) and adulthood (last 10 y), as was lifetime occupational activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence limits (OR (95% CL)) while controlling for confounders. Risk was reduced for exercise only in adolescence (OR = 0.84 (0.70–1.00)); exercise only in adulthood (OR = 0.68 (0.53–0.88)), and was further reduced for exercise in both adolescence and adulthood (OR = 0.47 (0.36–0.62)). Graded reductions in risk were noted with increasing years of exercise participation (OR1–5 yrs= 0.81 (0.67–0.94); OR6–10 yrs= 0.74 (0.59–0.93); OR11–15 yrs= 0.55 (0.38–0.79); OR16 + yrs= 0.40 (0.27–0.60);Ptrend,< 0.01). Lifetime occupational activity also was inversely related to risk (Ptrend< 0.01). These findings demonstrate that consistently high activity levels throughout life reduce breast cancer risk. Furthermore, they suggest that women may reduce their risk by increasing their activity levels in adulthood.

title: Influence of Physical Activity in Different Age and Life Periods on the Risk of Breast Cancer
abstract: We conducted a population-based case-control study of 1,237 incident breast cancer cases and 1,241 controls in Alberta between 1995 and 1997 to examine the effect of physical activity performed at different ages and life periods on breast cancer risk. In this study, we measured all types of physical activity done throughout life with a questionnaire developed and tested specifically for this study. We found that breast cancer risk was most associated with a risk reduction for activity done later in life, particularly between menopause and the reference year, for which we observed an odds ratio of 0.70 (95% confidence interval = 0.52–0.95). We also stratified the study participants into four categories according to their patterns of physical activity performed before and after menopause. For the women who sustained physical activity throughout life vs those who were never active, we found an odds ratio of 0.58 (95% confidence interval = 0.41–0.83). This study suggests that sustained activity throughout life and particularly activity done later in life may have the most benefit in reducing breast cancer risk.

title: Physical activity and breast cancer risk in women aged 20-54 years.
abstract: Although several studies have suggested that physical activity is associated with a decreased risk of breast cancer, such a decrease has not been found consistently, perhaps because physical activity was assessed in different ways and for restricted periods. Few studies have assessed the risk of breast cancer in relation to lifetime physical activity. We used data from a population-based, case-control study, including 918 case subjects (aged 20-54 years) and 918 age-matched population control subjects, to examine associations between breast cancer risk and physical activity at ages 10-12 years and 13-15 years, lifetime recreational activity, and title of longest held job.



Women who were more active than their peers at ages 10-12 years had a lower risk of breast cancer (odds ratio [OR] = 0.68; 95% confidence interval [CI] = 0.49-0.94). Women who had ever engaged in recreational physical activity had a reduced risk of breast cancer compared with inactive women (OR = 0.70; 95% CI = 0.56-0.88). Neither very early recreational activity (before age 20 years) nor recent activity (last 5 years) was associated with a greater reduction in risk than recreational activity in the intermediate period. Furthermore, women who started recreational activities after age 20 years and women who started earlier and continued their activities throughout adult life experienced a similar reduction in risk. Lean women, i.e., women with a body mass index (weight in kg/[height in m](2)) less than 21. 8 kg/m(2), appeared to have a lower risk associated with recreational physical activity than women with a body mass index greater than 24.5 kg/m(2) (OR = 0.57 [95% CI = 0.40-0.82] and OR = 0. 92 [95% CI = 0.65-1.29], respectively).



Our findings support the hypothesis that recreational physical activity is associated with a decreased risk of breast cancer. Physical activity in early or recent life does not appear to be associated with additional beneficial effects.