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Background: Physical activity is associated with lower risk for endometrial cancer, but the extent to which the association is mediated by body mass index (BMI) in midlife is unclear. This study describes the physical activity-endometrial cancer association and whether BMI mediates this relationship., Methods: Participants were 67 705 women in the National Institutes of Health-AARP Diet and Health Study (50-71 years) who recalled their physical activity patterns starting at age 15-18 years. We identified 5 long-term physical activity patterns between adolescence and cohort entry (ie, inactive, maintained low, maintained high, increasers, decreasers). We used Cox regression to assess the relationship between these patterns and midlife BMI and endometrial cancer, adjusting for covariates. Mediation analysis was used to estimate the proportion of the physical activity-endometrial cancer association that was mediated by midlife BMI., Results: During an average 12.4 years of follow-up 1468 endometrial cancers occurred. Compared with long-term inactive women, women who maintained high or increased activity levels had a 19% to 26% lower risk for endometrial cancer (maintained high activity: hazard ratio = 0.81, 95% confidence interval [CI] = 0.67 to 0.98; increasers: hazard ratio = 0.74, 95% CI = 0.61 to 0.91). They also had a 50% to 77% lower risk for obesity in midlife (eg, maintained high activity: odds ratio for a BMI of 30-39.9 kg/m 2 = 0.50, 95% CI = 0.46 to 0.55; and maintained high activity, odds ratio for a BMI of ≥40 kg/m 2 = 0.32, 95% CI = 0.26 to 0.39). BMI was a statistically significant mediator accounting for 55.5% to 62.7% of the physical activity-endometrial cancer associations observed., Conclusions: Both maintaining physical activity throughout adulthood and adopting activity later in adulthood can play a role in preventing obesity and lowering the risk for endometrial cancer., (Published by Oxford University Press 2021. This work is written by US Government employees and is in the public domain in the US.)

Background: Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study., Methods: Among 153 730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16 896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression., Results: BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA., Conclusions: Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding., (Published by Oxford University Press on behalf of the International Epidemiological Association 2018. This work is written by US Government employees and is in the public domain in the US.)

Purpose: To investigate associations between accelerometer-determined sedentary time (ST) in prolonged (≥30 min) and nonprolonged (<30 min) bouts with physical activity energy expenditure (PAEE) from doubly labeled water. Additionally, associations between ST and body mass index (BMI) and waist circumference were examined., Methods: Data from 736 women and 655 men age 43 to 82 yr were analyzed. Participants wore the Actigraph GT3X for 7 d on two occasions approximately 6 months apart, and the average of the measurements was used. Physical activity energy expenditure was estimated by subtracting resting metabolic rate and the thermic effect of food from doubly labeled water estimates of total daily energy expenditure. Cross-sectional associations were analyzed using isotemporal substitution modeling., Results: Reallocation of prolonged ST to nonprolonged was not associated with increased PAEE and only significantly associated with lower BMI (β = -0.57 kg·m; 95% confidence interval, -0.94 to -0.20) and waist circumference (β = -1.61 cm; 95% confidence interval, -2.61 to -0.60) in men. Replacing either type of ST with light or moderate-to-vigorous physical activity was significantly associated with higher PAEE, and lower BMI and waist circumference in both women and men., Conclusions: Limiting time spent sedentary as well as decreasing ST accumulated in prolonged bouts may have beneficial effects on BMI and waist circumference. Replacing any type of ST with activities of light or higher intensity may also have a substantial impact on PAEE.

Background: Elevated body mass index (BMI) is associated with increased risk of postmenopausal breast cancer. The underlying mechanisms, however, remain elusive., Methods: In a nested case-control study of 621 postmenopausal breast cancer case participants and 621 matched control participants, we measured 617 metabolites in prediagnostic serum. We calculated partial Pearson correlations between metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni-corrected α level for 617 statistical tests = P < 8.10 × 10-5) in relation to invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs 10th percentile (modeled on a continuous basis) were estimated using conditional logistic regression while controlling for breast cancer risk factors, including BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were mutually adjusted for one another to determine those independently associated with breast cancer risk., Results: Of 67 BMI-associated metabolites, two were independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3-methylglutarylcarnitine (OR = 1.67, 95% CI = 1.21 to 2.30). Four metabolites were independently associated with estrogen receptor-positive (ER+) breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.84, 95% CI = 1.27 to 2.67), 3-methylglutarylcarnitine (OR = 1.91, 95% CI = 1.23 to 2.96), allo-isoleucine (OR = 1.76, 95% CI = 1.23 to 2.51), and 2-methylbutyrylcarnitine (OR = 1.89, 95% CI = 1.22 to 2.91). In a model without metabolites, each 5 kg/m2 increase in BMI was associated with a 14% higher risk of breast cancer (OR = 1.14, 95% CI = 1.01 to 1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine weakened this association (OR = 1.06, 95% CI = 0.93 to 1.20), with the logOR attenuating by 57.6% (95% CI = 21.8% to 100.0+%)., Conclusion: These four metabolites may signal metabolic pathways that contribute to breast carcinogenesis and that underlie the association of BMI with increased postmenopausal breast cancer risk. These findings warrant further replication efforts.

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women's Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with <25 kg/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support the hypothesis that higher BMI after endometrial cancer diagnosis is associated with poorer survival., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Endometrial cancer (EC) survivors are the second largest group of female cancer survivors in the USA, with high prevalence of obesity and physical inactivity. While higher pre-diagnosis body mass index (BMI) has been associated with higher all-cause and disease-specific mortality, pre-diagnosis physical activity has shown mixed evidence of an association with mortality. However, the association between BMI, physical activity, and TV viewing measured after diagnosis and mortality risk among EC survivors is unknown., Methods: We identified 580 women with EC in the NIH-AARP Diet and Health Study who completed a post-diagnosis questionnaire on BMI, leisure time moderate- to vigorous-intensity physical activity (MVPA), and TV viewing. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality., Results: With a median follow-up time of 7.1 years, we observed 91 total deaths. We found a positive association between BMI ([Formula: see text] = 2.14, 95% CI 1.08-4.24 and mortality, and no statistically significant association between TV viewing (HR 5+ vs. <3 h/day  = 1.46, 95% CI 0.86-2.46) and mortality nor MVPA with mortality (HR 15+ vs. 0 MET h/week  = 0.72, 95% CI 0.43-1.21) after adjusting for tumor characteristics and demographic factors. Further adjustment for lifestyle and health status attenuated BMI associations ([Formula: see text] = 1.47, 95% CI 0.71-3.07), but strengthened the association between TV viewing and mortality (HR 5+ vs. <3 h/day  = 2.28, 95% CI 1.05-4.95)., Conclusions: Our results suggest that higher post-diagnosis BMI and TV viewing may be associated with higher mortality risk among EC patients, but that there may be complicated interrelationships between lifestyle factors of BMI, PA, and TV viewing and the mediating role of health status that need to be clarified.

Purpose: We aimed to determine whether baseline sedentary behavior was associated with changes in body mass index (BMI) over 9 yr., Methods: Participants were enrolled into the National Institutes of Health American Association of Retired Persons (NIH-AARP) Diet and Health study in 1995-1996 (median age, 63 yr), and BMI was reported at baseline and 9 yr later (n = 158,436). Sitting time (<3 (referent), 3-4, 5-6, 7-8, or ≥9 h·d), television viewing (none, <1, 1-2, 3-4, 5-6, 7-8, or ≥9 h·d), and the covariates (age, sex, race, education, smoking, moderate-to-vigorous physical activity, caloric intake, and sleep duration) were reported at baseline. We used longitudinal quantile regression to model changes at the 10th, 25th, 50th, 75th, and 90th BMI percentiles., Results: More sitting at baseline was associated with additional increases in BMI over time, and the association was stronger at the upper BMI percentiles (e.g., <3 (referent) vs 5-6 h·d of sitting additional increases: 50th percentile = 0.41 kg·m and 95% confidence interval (CI) = 0.34-0.48; 90th percentile = 0.85 kg·m and 95% CI = 0.72-0.98). Similar associations were observed between more television viewing at baseline and additional increases in BMI over time (e.g., no television (referent) vs 3-4 h·d of television: 50th percentile = 1.96 kg·m and 95% CI = 1.77-2.15; 90th percentile = 2.11 kg·m and 95% CI = 1.49-2.73)., Conclusions: Reducing sedentary behavior could help prevent an increase in BMI in adulthood especially at the upper percentiles of the BMI distribution and thereby reduce the prevalence of obesity.

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995-2009; Adventist Health Study 2, 2002-2008; Black Women's Health Study, 1995-2009; Cancer Prevention Study II, 1982-2008; Multiethnic Cohort Study, 1993-2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993-2009; Southern Community Cohort Study, 2002-2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30-104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25-27.4, 27.5-29.9, 30-34.9, 35-39.9, 40-49.9, and 50-60 kg/m(2) were 1.02 (0.92-1.12), 1.06 (0.95-1.18), 1.32 (1.18-1.47), 1.54 (1.29-1.83), 1.93 (1.46-2.56), and 1.93 (0.80-4.69), respectively among men and 1.06 (0.99-1.15), 1.15 (1.06-1.25), 1.24 (1.15-1.34), 1.58 (1.43-1.74), 1.80 (1.60-2.02), and 2.31 (1.74-3.07) respectively among women (reference category 22.5-24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

Both short and long durations of sleep are associated with higher mortality, but little is known about the interrelationship between sleep and other modifiable factors in relation to mortality. In the National Institutes of Health-AARP Diet and Health Study (1995-1996), we examined associations between sleep duration and total, cardiovascular disease (CVD), and cancer mortality among 239,896 US men and women aged 51-72 years who were free of cancer, CVD, and respiratory disease. We evaluated the influence of moderate-to-vigorous physical activity, television viewing, and body mass index (BMI; weight (kg)/height (m)(2)) on the sleep-mortality association and assessed their combined association with mortality. During an average of 14 years of follow-up, we identified 44,100 deaths. Compared with 7-8 hours of sleep per day, both shorter and longer sleep durations were associated with higher total and CVD mortality. We found a greater elevation in CVD mortality associated with shorter sleep among overweight and obese people, suggesting a synergistic interaction between sleep and BMI. People in the unhealthy categories of all 4 risk factors (sleep <7 hours/day, moderate-to-vigorous physical activity ≤1 hour/week, television viewing ≥3 hours/day, and BMI ≥25) had significantly higher all-cause (relative risk (RR) = 1.42, 95% confidence interval (CI): 1.34, 1.52), CVD (RR = 1.90, 95% CI: 1.67, 2.17), and cancer (RR = 1.21, 95% CI: 1.09, 1.34) mortality. Short sleep duration may predict higher mortality, particularly CVD mortality, among overweight and obese people., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical activity with incidence of COPD., Methods: We obtained data on anthropometric measurements and physical activity from 113,279 participants in the National Institutes of Health-AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995-1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables., Results: Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index [BMI] ≥ 35) and underweight (BMI < 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk [RR] 1.56, 95% confidence interval [CI] 1.15-2.11). Larger waist circumference (highest v. normal categories, adjusted RR 1.72, 95% CI 1.37-2.16) and higher waist-hip ratio (highest v. normal categories, adjusted RR 1.46, 95% CI 1.23-1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% CI 0.62-0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RR 0.71, 95% CI 0.63-0.79) were inversely associated with COPD., Interpretation: Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD., (© 2014 Canadian Medical Association or its licensors.)

Objective: In a large prospective cohort, we examined the relationship of body mass index (BMI) with mortality among blacks and compared the results to those among whites in this population., Design and Methods: The study population consisted of 7,446 non-Hispanic black and 130,598 white participants, ages 49-78 at enrollment, in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. BMI at baseline, BMI at age 20, and BMI change were calculated using self-reported and recalled height and weight. Relative risks were stratified by race and sex and adjusted for age, education, marital status, and smoking., Results: During follow-up, 1,495 black and 18,236 white participants died (mean = 13 years). Clear J-shaped associations between BMI and mortality were observed among white men and women. Among black men and women, the bottoms of these curves were flatter, and increasing risks of death with greater BMI were observed only at higher BMI levels (≥35.0). Associations for BMI at age 20 and BMI change also appeared to be stronger in magnitude in whites versus blacks, and these racial differences appeared to be more pronounced among women., Conclusion: Our results suggest that BMI may be more weakly associated with mortality in blacks, particularly black women, than in whites., (Copyright © 2013 The Obesity Society.)

Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995-1996; n = 485,049), and a subset of participants completed a second questionnaire (1996-1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m(2) increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk.

Background Higher body mass index (BMI) and inactivity have been associated with a higher risk of developing endometrial cancer, but the impact on endometrial cancer survival is unclear. Methods Among incident endometrial cancer case subjects in the National Institutes of Health-AARP Diet and Health Study, we examined associations of prediagnosis BMI (n = 1400) and physical activity (n = 875) with overall and disease-specific 5- and 10-year mortality. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for tumor characteristics, treatment, and other risk factors. All statistical tests were two-sided. Results Compared with women with a BMI in the range of 18.5 to less than 25kg/m(2), the hazard ratios for 5-year all-cause mortality were 1.74 (95% CI = 1.13 to 2.66) for BMI in the range of 25 to less than 30kg/m(2), 1.84 (95% CI = 1.17 to 2.88) for BMI in the range of 30 to less than 35kg/m(2), and 2.35 (95% CI = 1.48 to 3.73) for BMI greater than or equal to 35kg/m(2) (P trend < .001). Higher BMI was also statistically significantly associated with poorer endometrial cancer-specific but not cardiovascular disease 5-year mortality. Hazard ratio estimates for 10-year all-cause and endometrial cancer-specific mortality as related to BMI were similar to 5-year hazard ratio estimates, whereas 10-year cardiovascular disease mortality became statistically significant (HR = 4.08; 95% CI = 1.56 to 10.71 comparing extreme BMI groups). More physical activity was related to lower all-cause 5-year mortality (HR = 0.57, 95% CI = 0.33 to 0.98 for >7 hours/week vs never/rarely), but the association was attenuated after adjustment for BMI (HR = 0.64, 95% CI = 0.37 to 1.12). No association was observed between physical activity and disease-specific mortality. Conclusions Our findings suggest that higher prediagnosis BMI increases risk of overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowers risk. Intervention studies of the effect of these modifiable lifestyle factors on mortality are needed.

Background: Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis., Methods and Findings: We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21-90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3-4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report., Conclusions: More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. Please see later in the article for the Editors' Summary.

Purpose: Adiponectin is a promising biomarker linking obesity and disease risk; however, limited data are available regarding adiponectin in black women among whom obesity is highly prevalent., Methods: A cross-sectional analysis was conducted to assess racial differences and correlates of serum adiponectin measured in 996 black and 996 white women enrolled in the Southern Community Cohort Study through Community Health Centers in 12 southeastern states from 2002 to 2006., Results: Black subjects had significantly lower adiponectin levels than white subjects (median 10.9 vs 14.9 μg/mL, Wilcoxon p < .0001). Among black subjects, adiponectin was lower among overweight and obese women compared with healthy weight women but showed no clear decreasing trend with increasing severity of obesity; adjusted geometric means (95% confidence interval) were 15.0 [13.8-16.4], 11.5 [10.6-12.5], 9.7 [9.0-10.6], 11.4 [10.3-12.6], and 10.9 [9.5-12.6] μg/mL for body mass index [BMI] categories of 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40-45, p for trend <.0001). In contrast, among whites there was a monotonic reduction in adiponectin over increasing BMI (adjusted geometric means = 19.9 [18.3-21.7], 15.1 [13.9-16.4], 14.3 [13.2-15.5], 12.5 [11.2-13.9], and 11.0 [9.7-12.5] μg/mL, p for trend <.0001). BMI, age, high-density lipoprotein cholesterol, and hypertension were important correlates of adiponectin in both groups., Conclusions: Among women, racial differences exist in both the magnitude and form of the adiponectin-BMI association., (Copyright © 2011 Elsevier Inc. All rights reserved.)

African-American (AA) race/ethnicity, lower body mass index (BMI), and higher IGF1 levels are associated with premenopausal breast cancer risk. This cross-sectional analysis investigated whether BMI or BMI at age 21 years contributes to racial differences in IGF1, IGF2, IGF-binding protein 3 (IGFBP3), or free IGF1. Participants included 816 white and 821 AA women between ages 40 and 79 years across a wide BMI range (18.5-40 kg/m(2)). Compared with white women, AA women had higher mean IGF1 (146.3 vs 134.4 ng/ml) and free IGF1 (0.145 vs 0.127) levels, and lower IGF2 (1633.0 vs 1769.3 ng/ml) and IGFBP3 (3663.3 vs 3842.5 ng/ml) levels (all P<0.01; adjusted for age, height, BMI, BMI at age 21 years, and menopausal status). Regardless of race, IGF1 and free IGF1 levels rose sharply as BMI increased to 22-24 kg/m(2), and then declined thereafter, while IGF2 and IGFBP3 levels tended to rise with BMI. In contrast, BMI at age 21 years was inversely associated with all IGF levels, but only among white women (P-interaction=0.01). With the decline in IGF1 with BMI at age 21 years among whites, racial differences in IGF1 significantly increased among women who were obese in early adulthood. In summary, BMI was associated with IGF1 levels regardless of race/ethnicity, while obesity during childhood or young adulthood may have a greater impact on IGF1 levels among white women. The effects of obesity throughout life on the IGF axis and racial differences in breast cancer risk require study.

Objectives: Physical activity has demonstrable effects on estrogen levels in pre- and postmenopausal women. Increased oxidation of estrone to 2-hydroxyestrone (2HE) relative to 16alpha-hydroxyestrone (16HE) has been hypothesized to reduce breast cancer risk, but little is known about the effect of physical activity and body size in relation to the ratio of 2HE and 16HE in women. We examined these relationships in cross-sectional analyses of 157 North American and Chinese women., Methods: Physical activity was assessed using validated questionnaires. Adiposity was assessed as body mass index (BMI, kg/m2) and by anthropometric methods (% body fat). Estrone metabolites, 2HE and 16HE, were determined from urine via ELISA., Results: Regression analyses on the 2HE/16HE ratio revealed an interaction between leisure-time physical activities and adiposity in both North American and Chinese women (p < or = 0.05). Women reporting low levels of leisure-time physical activity who had higher BMI levels had 2HE/16HE ratios that were lower than their lean counterparts. In contrast, women with higher BMI levels that were physically active maintained higher 2HE/16HE ratios., Conclusion: These findings suggest that physical activity participation has the potential to modify the adverse effect of increased adiposity on estrogen metabolism in North American and Chinese women., (Copyright 2004 Kluwer Academic Publishers)

Unlabelled: Elevated high-sensitivity c-reactive protein (hs-CRP) is associated with increased risk of future first and recurrent coronary events and has been associated with both high body mass index (BMI) and low physical activity in cross sectional studies., Purpose: To longitudinally examine the effects of BMI and both current and previous-year physical activity on hs-CRP in healthy men and women (N = 109)., Methods: BMI and hs-CRP were measured five times (baseline and quarterly) over 1 yr. Current physical activity was assessed 12-15 times during the study via 24-h recall. Previous-year physical activity was assessed using the Baecke questionnaire at baseline., Results: Mean BMI and hs-CRP were unchanged over the course of the study, but current physical activity increased on visit 3. Average hs-CRP was not related to average current physical activity or to natural changes in current physical activity across the five visits. Additionally, current physical activity on any given visit was not associated with hs-CRP on the following visit. When current physical activity, BMI, age, gender, and smoking were included in the statistical model, only BMI was significantly related to hs-CRP (P < 0.001). Average hs-CRP was significantly correlated with average BMI (r = 0.50; P < 0.001) but was not related to previous-year (Baecke) physical activity levels (r = 0.02; P = 0.89). When subjects were grouped by BMI (<25 kg.m-2, 25-29.9 kg x m-2, >30 kg x m-2) hs-CRP was significantly greater in obese (3.2 +/- 1.9 mg.L-1) and overweight (2.1 +/- 1.7 mg x L-1) than normal weight (1.1 +/- 1.0 mg.L-1) subjects (ANOVA P < 0.05). Current physical activity was similar between the three BMI groups at all times, and was unrelated to hs-CRP in all groups, throughout the study period., Conclusion: These data indicate that BMI, but not previous-year or current physical activity, predicts hs-CRP.

Purpose: Physical activity levels (PAL) are associated with mortality risk and were instrumental in estimating national energy requirements, but we are unaware of population-based estimates of PAL in US adults. Thus, we conducted a nationwide survey using a validated previous-day recall method to estimate PAL and the behavioral determinants of low and higher PAL. Methods: Participants from the AmeriSpeak panel 20–75 yr of age (N = 2640) completed Activities Completed over Time in 24-hours previous-day recalls. PAL values were estimated as the average metabolic equivalent value over 24 h. Recalls were conducted on randomly selected days in October and November 2019. Survey sample design weights were applied to reflect the US population. Results: Mean age was 45.3 yr, 51% were female, 67% were non-Hispanic White, and 37% had a body mass index of ≥30 kg·m−2. US adults reported a mean PAL of 1.63 (95% confidence interval, 1.60–1.65), and 39% (37%–42%) of adults reported PAL ≥1.6 on a given day. Men reported higher PAL than women (1.67 vs 1.59), and older adults reported lower PAL. Adults with PAL <1.4 spent 81% (12.1 h·d−1) of their waking day sedentary and 19% (2.7 h·d−1) in total physical activity. Adults with PAL considered to be "active"(1.6–1.89) spent only 49% (8.0 h·d−1) of their waking day sedentary, and 51% (8.3 h·d−1) physically active. Conclusions: Our study provides novel estimates of PAL in a nationwide sample of US adults and a description of the type and intensity of sedentary and physically active behaviors contributing to low and higher PAL. These findings may inform public health messages aimed at increasing physical activity in adults and potentially contribute to obesity prevention efforts. [ABSTRACT FROM AUTHOR]

Background: Obesity is correlated with many biomarkers, but the extent to which these correlate with underlying body composition is poorly understood.Objectives: Our objectives were to 1) describe/compare distinct contributions of fat/lean mass with BMI-metabolite correlations and 2) identify novel metabolite biomarkers of fat/lean mass.Methods: The Alberta Physical Activity and Breast Cancer Prevention Trial was a 2-center randomized trial of healthy, inactive, postmenopausal women (n = 304). BMI (in kg/m2) was calculated using weight and height, whereas DXA estimated fat/lean mass. Ultra-performance liquid chromatography and mass spectrometry measured relative concentrations of serum metabolite concentrations. We estimated partial Pearson correlations between 1052 metabolites and BMI, adjusting for age, smoking, and site. Fat mass index (FMI; kg/m2) and lean mass index (LMI; kg/m2) correlations were estimated similarly, with mutual adjustment to evaluate independent effects.Results: Using a Bonferroni-corrected α level <4.75 × 10-5,  we observed 53 BMI-correlated metabolites (|r| = 0.24-0.42). Of those, 21 were robustly correlated with FMI (|r| > 0.20), 25 modestly (0.10 ≤ |r| ≤ 0.20), and 7 virtually null (|r| < 0.10). Ten of 53 were more strongly correlated with LMI than with FMI. Examining non-BMI-correlated metabolites, 6 robustly correlated with FMI (|r| = 0.24-0.31) and 2 with LMI (r = 0.25-0.26). For these, correlations for fat and lean mass were in opposing directions compared with BMI-correlated metabolites, in which correlations were mostly in the same direction.Conclusions: Our results demonstrate how a thorough evaluation of the components of fat and lean mass, along with BMI, provides a more accurate assessment of the associations between body composition and metabolites than BMI alone. Such an assessment makes evident that some metabolites correlated with BMI predominantly reflect lean mass rather than fat, and some metabolites related to body composition are not correlated with BMI. Correctly characterizing these relations is important for an accurate understanding of how and why obesity is associated with disease. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Introduction: Ample data support that leisure time aerobic moderate to vigorous physical activity (MVPA) is associated with lower risk of at least seven types of cancer. However, the link between muscle-strengthening activities and cancer etiology is not well understood. Our objective was to determine the association of weight lifting with incidence of 10 common cancer types. Methods: We used multivariable Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association of weight lifting with incidence of 10 cancer types in the National Institutes of Health-American Association of Retired Persons Diet and Health Study follow-up. Weight lifting was modeled continuously and categorically. Dose–response relationships were evaluated using cubic restricted spline models. We explored whether associations varied by subgroups defined by sex, age, and body mass index using the Wald test for homogeneity. We examined joint categories of MVPA and weight lifting in relation to cancer risk for significant associations. Results: After adjusting for all covariates including MVPA, we observed a statistically significant lower risk of colon cancer (P trend = 0.003) in individuals who weight lifted; the HR and 95% CI associated with low and high weight lifting as compared with no weight lifting were 0.75 (95% CI, 0.66–0.87) and 0.78 (95% CI, 0.61–0.98), respectively. The weight lifting-colon cancer relationship differed between men and women (any weight lifting vs no weight lifting: HRmen = 0.91; 95% CI, 0.84–0.98; HRwomen = 1.00; 95% CI, 0.93–1.08; P interaction = 0.008). A lower risk of kidney cancer among weight lifters was observed but became nonsignificant after adjusting for MVPA (P trend = 0.06), resulting in an HR of 0.94 (95% CI, 0.78–1.12) for low weight lifting and 0.80 (95% CI, 0.59–1.11) for high weight lifting. Conclusions: Participants who engaged in weight lifting had a significantly lower risk of colon cancer and a trend toward a lower risk of kidney cancer than participants who did not weight lift. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of objectively measured levels of physical activity and sedentary time with major blood cell counts (e.g. white blood cells, red blood cells, platelets) among adults. Methods: Data collected from the 2003–2004 and 2005–2006 cycles of the National Health and Nutrition Examination Survey (NHANES) was used to assess blood cell counts in relation to objectively measured physical activity and sedentary time (accelerometer). A series of linear regressions modes were used to assess these associations adjusting for a range of factors known to be associated with blood cell counts, including age, body mass index, dietary factors, and previous infections. Results: Higher levels of moderate-vigorous physical activity (ptrend<0.001) and lower sedentary time (ptrend = 0.040) were associated with lower white blood cell counts. Conclusion: These results suggest that modifiable health behaviors, such as physical activity and sedentary time, may be associated with inflammatory status through white blood cell counts, which may be important for future disease risk. [ABSTRACT FROM AUTHOR]

Background: The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.Methods: We examined associations of body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) with lung cancer risk among 1.6 million Americans, Europeans, and Asians. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Analyses for WC/WHR were further adjusted for BMI. The joint effect of BMI and WC/WHR was also evaluated.Results: During an average 12-year follow-up, 23 732 incident lung cancer cases were identified. While BMI was generally associated with a decreased risk, WC and WHR were associated with increased risk after controlling for BMI. These associations were seen 10 years before diagnosis in smokers and never smokers, were strongest among blacks, and varied by histological type. After excluding the first five years of follow-up, hazard ratios per 5 kg/m2 increase in BMI were 0.95 (95% CI = 0.90 to 1.00), 0.92 (95% CI = 0.89 to 0.95), and 0.89 (95% CI = 0.86 to 0.91) in never, former, and current smokers, and 0.86 (95% CI = 0.84 to 0.89), 0.94 (95% CI = 0.90 to 0.99), and 1.09 (95% CI = 1.03 to 1.15) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Hazard ratios per 10 cm increase in WC were 1.09 (95% CI = 1.00 to 1.18), 1.12 (95% CI = 1.07 to 1.17), and 1.11 (95% CI = 1.07 to 1.16) in never, former, and current smokers, and 1.06 (95% CI = 1.01 to 1.12), 1.20 (95% CI = 1.12 to 1.29), and 1.13 (95% CI = 1.04 to 1.23) for adenocarcinoma, squamous cell, and small cell carcinoma, respectively. Participants with BMIs of less than 25 kg/m2 but high WC had a 40% higher risk (HR = 1.40, 95% CI = 1.26 to 1.56) than those with BMIs of 25 kg/m2 or greater but normal/moderate WC.Conclusions: The inverse BMI-lung cancer association is not entirely due to smoking and reverse causation. Central obesity, particularly concurrent with low BMI, may help identify high-risk populations for lung cancer. [ABSTRACT FROM AUTHOR]

Background: The relations of physical activity and sedentary behavior to mortality risk among patients with renal cell cancer have not yet been evaluated. Methods: We conducted a prospective cohort study among 667 renal cell cancer survivors aged 50–71 years of the National Institutes of Health (NIH)-AARP Diet and Health Study with a median follow-up time of 7.1 years. Post-diagnosis physical activity, TV viewing, and total sitting time were assessed using self-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards models. Results: Increasing levels of moderate to vigorous physical activity were related to decreased risk of overall mortality [multivariable-adjusted HRs for <1 hr/wk (reference), 1 to 3 hrs/wk, ≥3 to <7 hrs/wk, and ≥7 hrs/wk = 1.0, 1.16, 0.94, and 0.60 (95% CI = 0.38–0.96; p-trend = 0.03)]. In contrast, television viewing was associated with increased risk of overall mortality in the age- and sex-adjusted model (HR for >4 hrs/d vs. 0 to 2 hrs/d = 1.52, 95% CI = 1.02–2.26; p-trend = 0.04), but the relation was attenuated following further control for other covariates (multivariable-adjusted HR = 1.44, 95% CI = 0.92–2.24; p-trend = 0.11). Total sitting time was unrelated to all-cause mortality. Conclusion: Among renal cancer patients, moderate to vigorous physical activity is associated with decreased risk of overall mortality. Clinicians should consider discussing the potential benefits of physical activity for longevity among survivors of renal cell cancer. [ABSTRACT FROM AUTHOR]

Background: Elevated body mass index (BMI) is associated with increased risk of postmenopausal breast cancer. The underlying mechanisms, however, remain elusive.Methods: In a nested case-control study of 621 postmenopausal breast cancer case participants and 621 matched control participants, we measured 617 metabolites in prediagnostic serum. We calculated partial Pearson correlations between metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni-corrected α level for 617 statistical tests = P < 8.10 × 10-5) in relation to invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs 10th percentile (modeled on a continuous basis) were estimated using conditional logistic regression while controlling for breast cancer risk factors, including BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were mutually adjusted for one another to determine those independently associated with breast cancer risk.Results: Of 67 BMI-associated metabolites, two were independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3-methylglutarylcarnitine (OR = 1.67, 95% CI = 1.21 to 2.30). Four metabolites were independently associated with estrogen receptor-positive (ER+) breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.84, 95% CI = 1.27 to 2.67), 3-methylglutarylcarnitine (OR = 1.91, 95% CI = 1.23 to 2.96), allo-isoleucine (OR = 1.76, 95% CI = 1.23 to 2.51), and 2-methylbutyrylcarnitine (OR = 1.89, 95% CI = 1.22 to 2.91). In a model without metabolites, each 5 kg/m2 increase in BMI was associated with a 14% higher risk of breast cancer (OR = 1.14, 95% CI = 1.01 to 1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine weakened this association (OR = 1.06, 95% CI = 0.93 to 1.20), with the logOR attenuating by 57.6% (95% CI = 21.8% to 100.0+%).Conclusion: These four metabolites may signal metabolic pathways that contribute to breast carcinogenesis and that underlie the association of BMI with increased postmenopausal breast cancer risk. These findings warrant further replication efforts. [ABSTRACT FROM AUTHOR]

Background: Several anthropometric measures have been associated with hormone-related cancers. However, it is unknown whether estrogen metabolism plays an important role in these relationships. We examined whether measured current body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported BMI at age 18 years were associated with serum estrogens/estrogen metabolites using baseline, cross-sectional data from 1835 postmenopausal women enrolled in the Women's Health Initiative Observational Study.Methods: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means (GMs) of estrogens/estrogen metabolites (in picomoles per liter) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use.Results: Among never or former MHT users, current BMI (≥30 vs. <25 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM 432 vs. 239 pmol/L for estrone, 74 vs. 46 pmol/L for estradiol; p-trend < 0.001 for both) and all of the 2-, 4-, and 16-pathway estrogen metabolites evaluated (all p-trend ≤ 0.02). After additional adjustment for estradiol, unconjugated methylated 2-catechols were inversely associated (e.g., 2-methoxyestrone multivariable GM 9.3 vs. 12.0 pmol/L; p-trend < 0.001). Among current MHT users, current BMI was not associated with parent estrogens but was inversely associated with methylated catechols (e.g., 2-methoxyestrone multivariable GM 216 vs. 280 pmol/L; p-trend = 0.008). Similar patterns of association were found with WHR; however, the associations were not independent of BMI. Height and BMI at age 18 years were not associated with postmenopausal estrogens/estrogen metabolite levels.Conclusions: Our data suggest that postmenopausal BMI is associated with increased circulating levels of parent estrogens and reduced methylation of catechol estrogen metabolites, the estrogen metabolism patterns that have previously been associated with higher breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: Physical activity is associated with a variety of health benefits, but the biological mechanisms that explain these associations remain unclear. Metabolomics is a powerful tool to comprehensively evaluate global metabolic signature associated with physical activity and helps to pinpoint the pathways that mediate the health effects of physical activity. There has been limited research on metabolomics and habitual physical activity, and no metabolomics study has examined sedentary behaviour and physical activity of different intensities.Methods: In a group of Chinese adults (N = 277), we used an untargeted approach to examine 328 plasma metabolites in relation to accelerometer-measured physical activity, including overall volume of physical activity (physical activity energy expenditure (PAEE) and duration of physically active time) and sedentary time, and measures related to different intensities of physical activity (moderate-to-vigorous activity (MVPA), light activity, average physical activity intensity).Results: We identified 11 metabolites that were associated with total activity, with a false discovery rate of 0.2 or lower. Notably, we observed generally lower levels of amino acids in the valine, leucine and isoleucine metabolism pathway and of carbohydrates in sugar metabolism among participants with higher activity levels. Moreover, we found that PAEE, time spent in light activity and duration of physically active time were associated with a similar metabolic pattern, whereas the metabolic signature associated with sedentary time mirrored this pattern. In contrast, average activity intensity and time spent in MVPA appeared to be associated with somewhat different metabolic patterns.Conclusions: Overall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity. [ABSTRACT FROM AUTHOR]

Background: Several health agencies have issued guidelines promoting behaviors to reduce chronic disease risk; however, little is known about the impact of such guidelines, particularly on cancer incidence. Objective: The objective was to determine whether greater adherence to the American Cancer Society (ACS) cancer prevention guidelines is associated with a reduction in cancer incidence, cancer mortality, and total mortality. Design: The NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults aged 50-71 y at recruitment in 1995-1996, was followed for a median of 10.5 y for cancer incidence, 12.6 y for cancer mortality, and 13.6 y for total mortality. Participants who reported a history of cancer or who had missing data were excluded, yielding 476,396 subjects for analysis. We constructed a 5-level score measuring adherence to ACS guidelines, which included baseline body mass index, physical activity, alcohol intake, and several aspects of diet. Cox proportional hazards models were used to compute HRs and 95% CIs for the association of the adherence score with cancer incidence, cancer mortality, and total mortality. All analyses included fine adjustment for cigarette smoking. Results: Among 476,396 participants, 73,784 incident first cancers, 16,193 cancer deaths, and 81,433 deaths from all causes were identified in the cohort. Adherence to ACS guidelines was associated with reduced risk of all cancers combined: HRs (95% CIs) for the highest compared with the lowest level of adherence were 0.90 (0.87, 0.93) in men and 0.81 (0.77, 0.84) in women. Fourteen of 25 specific cancer sites showed a reduction in risk associated with increased adherence. Adherence was also associated with reduced cancer mortality [HRs (95% CIs) were 0.75 (0.70, 0.80) in men and 0.76 (0.70, 0.83) in women] and reduced all-cause mortality [HRs (95% CIs) were 0.74 (0.72, 0.76) in men and 0.67 (0.65, 0.70) in women]. Conclusions: In both men and women, adherence to the ACS guidelines was associated with reductions in all-cancer incidence and the incidence of cancer at specific sites, as well as with reductions in cancer mortality and total mortality. These data suggest that, after accounting for cigarette smoking, adherence to a set of healthy behaviors may have considerable health benefits. This trial was registered at www.clinicaltrials.gov as NCT00340015. [ABSTRACT FROM AUTHOR]

A high body mass index (BMI) is a major risk factor for several chronic diseases, but the biology underlying these associations is not well-understood. Dyslipidemia, inflammation, and elevated levels of growth factors and sex steroid hormones explain some of the increased disease risk, but other metabolic factors not yet identified may also play a role. In order to discover novel metabolic biomarkers of BMI, we used non-targeted metabolomics to assay 317 metabolites in blood samples from 947 participants and examined the cross-sectional associations between metabolite levels and BMI. Participants were from three studies in the United States and China. Height, weight, and potential confounders were ascertained by questionnaire (US studies) or direct measurement (Chinese study). Metabolite levels were measured using liquid-phase chromatography and gas chromatography coupled with mass spectrometry. We evaluated study-specific associations using linear regression, adjusted for age, gender, and smoking, and we estimated combined associations using random effects meta-analysis. The meta-analysis revealed 37 metabolites significantly associated with BMI, including 19 lipids, 12 amino acids, and 6 others, at the Bonferroni significance threshold ( P < 0.00016). Eighteen of these associations had not been previously reported, including histidine, an amino acid neurotransmitter, and butyrylcarnitine, a lipid marker of whole-body fatty acid oxidation. Heterogeneity by study was minimal (all P > 0.05). In total, 110 metabolites were associated with BMI at the P < 0.05 level. These findings establish a baseline for the BMI metabolome, and suggest new targets for researchers attempting to clarify mechanistic links between BMI and disease risk. [ABSTRACT FROM AUTHOR]

Purpose Gathering contextual information (i.e., location and purpose) about active and sedentary behaviors is an advantage of self-report tools such as previous day recalls (PDR). However, the validity of PDR's for measuring context has not been empirically tested. The purpose of this paper was to compare PDR estimates of location and purpose to direct observation (DO). Methods Fifteen adult (18-75 y) and 15 adolescent (12-17 y) participants were directly observed during at least one segment of the day (i.e., morning, afternoon or evening). Participants completed their normal daily routine while trained observers recorded the location (i.e., home, community, work/school), purpose (e.g., leisure, transportation) and whether the behavior was sedentary or active. The day following the observation, participants completed an unannounced PDR. Estimates of time in each context were compared between PDR and DO. Intra-class correlations (ICC), percent agreement and Kappa statistics were calculated. Results For adults, percent agreement was 85% or greater for each location and ICC values ranged from 0.71 to 0.96. The PDR-reported purpose of adults' behaviors were highly correlated with DO for household activities and work (ICCs of 0.84 and 0.88, respectively). Transportation was not significantly correlated with DO (ICC = -0.08). For adolescents, reported classification of activity location was 80.8% or greater. The ICCs for purpose of adolescents' behaviors ranged from 0.46 to 0.78. Participants were most accurate in classifying the location and purpose of the behaviors in which they spent the most time. Conclusions This study suggests that adults and adolescents can accurately report where and why they spend time in behaviors using a PDR. This information on behavioral context is essential for translating the evidence for specific behavior-disease associations to health interventions and public policy. [ABSTRACT FROM AUTHOR]

The relationship between sleep and obesity or weight gain in adults, particularly older populations, remains unclear. In a cohort of 83,377 US men and women aged 51–72 years, we prospectively investigated the association between self-reported sleep duration and weight change over an average of 7.5 years of follow-up (1995–2004). Participants were free of cancer, heart disease, and stroke at baseline and throughout the follow-up. We observed an inverse association between sleep duration per night and weight gain in both men (P for trend = 0.02) and women (P for trend < 0.001). Compared with 7–8 hours of sleep, shorter sleep (<5 hours or 5–6 hours) was associated with more weight gain (in kilograms; men: for <5 hours, β = 0.66, 95% confidence interval (CI): 0.19, 1.13, and for 5–6 hours, β = 0.12, 95% CI: −0.02, 0.26; women: for <5 hours, β = 0.43, 95% CI: 0.00, 0.86, and for 5–6 hours, β = 0.23, 95% CI: 0.08, 0.37). Among men and women who were not obese at baseline, participants who reported less than 5 hours of sleep per night had an approximately 40% higher risk of developing obesity than did those who reported 7–8 hours of sleep (for men, odds ratio = 1.45, 95% CI: 1.06, 1.99; for women, odds ratio = 1.37, 95% CI: 1.04, 1.79). The association between short sleep and excess weight gain was generally consistent across different categories of age, educational level, smoking status, baseline body mass index, and physical activity level. [ABSTRACT FROM PUBLISHER]

Purpose: A previous-day recall (PDR) may be a less error-prone alternative to traditional questionnaire- based estimates of physical activity and sedentary behavior (e.g., past year), but the validity of the method is not established. We evaluated the validity of an interviewer administered PDR in adolescents (12-17 yr) and adults (18-71 yr). Methods: In a 7-d study, participants completed three PDR, wore two activity monitors, and completed measures of social desirability and body mass index. PDR measures of active and sedentary time was contrasted against an accelerometer (ActiGraph) by comparing both to a valid reference measure (activPAL) using measurement error modeling and traditional validation approaches. Results: Age- and sex-specific mixed models comparing PDR to activPAL indicated the following: 1) there was a strong linear relationship between measures for sedentary (regression slope, β1 = 0.80-1.13) and active time (β1 = 0.64-1.09), 2) person-specific bias was lower than random error, and 3) correlations were high (sedentary: r = 0.60-0.81; active: r = 0.52-0.80). Reporting errors were not associated with body mass index or social desirability. Models comparing ActiGraph to activPAL indicated the following: 1) there was a weaker linear relationship between measures for sedentary (β1 = 0.63-0.73) and active time (β1 = 0.61-0.72), (2) person-specific bias was slightly larger than random error, and (3) correlations were high (sedentary: r = 0.68-0.77; active: r = 0.57-0.79). Conclusions: Correlations between the PDR and the activPAL were high, systematic reporting errors were low, and the validity of the PDR was comparable with the ActiGraph. PDR may have value in studies of physical activity and health, particularly those interested in measuring the specific type, location, and purpose of activity- related behaviors. [ABSTRACT FROM AUTHOR]

Background Higher body mass index (BMI) and inactivity have been associated with a higher risk of developing endometrial cancer, but the impact on endometrial cancer survival is unclear. Methods Among incident endometrial cancer case subjects in the National Institutes of Health-AARP Diet and Health Study, we examined associations of prediagnosis BMI (n = 1400) and physical activity (n = 875) with overall and disease- specific 5- and 10-year mortality. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for tumor characteristics, treatment, and other risk factors. All statistical tests were two-sided. Results Compared with women with a BMI in the range of 18.5 to less than 25 kg/m²,the hazard ratios for 5-year all-cause mortality were 1.74 (95% CI = 1.13 to 2.66) for BMI in the range of 25 to less than 30 kg/m² 1.84 (95% CI = 1.17 to 2.88) for BMI in the range of 30 to less than 35 kg/m² and 2.35 (95% CI = 1.48 to 3.73) for BMI greater than or equal to 35 kg/m (Ptrend< .001). Higher BMI was also statistically significantly associated with poorer endometrial cancer-specific but not cardiovascular disease 5-year mortality. Hazard ratio estimates for 10-year all-cause and endometrial cancer-specific mortality as related to BMI were similar to 5-year hazard ratio estimates, whereas 10-year cardiovascular disease mortality became statistically significant (HR = 4.08; 95% CI = 1.56 to 10.71 comparing extreme BMI groups). More physical activity was related to lower all-cause 5-year mortality (HR = 0.57, 95% CI = 0.33 to 0.98 for >7 hours/week vs never/rarely), but the association was attenuated after adjustment for BMI (HR = 0.64, 95% CI = 0.37 to 1.12). No association was observed between physical activity and disease-specific mortality. Conclusions Our findings suggest that higher prediagnosis BMI increases risk of overall and disease-specific mortality among women diagnosed with endometrial cancer, whereas physical activity lowers risk. Intervention studies of the effect of these modifiable lifestyle factors on mortality are needed. [ABSTRACT FROM AUTHOR]

Despite a potential preventive effect of physical activity on hepatobiliary cancer, little information is available on the relation between the two. We studied the association between frequency of vigorous physical activity and hepatobiliary cancer among 507,897 participants of the NIH-AARP Diet and Health Study, aged 50-71 years at baseline in 1995/1996. During 10 years of follow-up, 628 incident cases of liver cancer and 317 cases of extrahepatic biliary tract cancer were registered. Physical activity levels were assigned according to the frequency of engagement in 20 min or more of vigorous physical activity per week: never/rarely (lowest level), less than once per week, 1-2 times per week, 3-4 times per week, 5 or more times per week (highest level). Using Cox regression, multivariate-adjusted relative risks (RR) comparing the highest with the lowest level of physical activity revealed a statistically significant decreased risk for liver cancer (RR = 0.64, 95 % confidence interval (CI) = 0.49-0.84, p-trend <0.001), particularly hepatocellular carcinoma (RR = 0.56, 95 % CI = 0.41-0.78, p-trend <0.001), independent of body mass index. By comparison, multivariate analyses indicated that physical activity was not statistically significantly associated with extrahepatic bile duct cancer (RR = 0.86, 95 % CI = 0.45-1.65), ampulla of Vater cancer (RR = 0.66, 95 % CI = 0.29-1.48), or gallbladder cancer (RR = 0.63, 95 % CI = 0.33-1.21). These results suggest a potential preventive effect of physical activity on liver cancer but not extrahepatic biliary tract cancer, independent of body mass index. [ABSTRACT FROM AUTHOR]

Background/Aims: Leptin may be an important link between obesity and many high-burden diseases, including cancer and cardiovascular disease, but leptin levels and correlates in individuals of diverse racial backgrounds have not been well characterized despite racial differences in incidence and mortality patterns for many obesity-related diseases. Methods: In a cross-sectional study of 915 white and 892 black women enrolled in the Southern Community Cohort Study (age 40-79 years, half postmenopausal), serum leptin levels were compared between the race groups and across categories of body mass index (BMI). Potential correlates of leptin were assessed via race-stratified linear regression models. Results: Blacks had higher unadjusted leptin levels than whites (geometric mean 22.4 vs. 19.0 ng/ml; p < 0.0001). Leptin increased with increasing BMI, and racial differences in leptin were most pronounced in women with BMI ≥25. Significant correlates of leptin included BMI, age, alcohol consumption, cigarette smoking, diabetes (both races) and fat consumption (black women only). Leptin remained higher in black women (22.7 vs. 18.8 ng/ml) after adjustment for these factors. Conclusions: Persistent racial differences in leptin concentrations exist after adjustment for BMI and other factors. Leptin assessment may be informative in future studies that investigate racial differences in the development of obesity-related diseases. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height (m)2) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002–2009) for associations with BMI and gene × environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (β = −0.04, 95% confidence interval: −0.06, −0.02; P = 5.76 × 10−5) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians. [ABSTRACT FROM AUTHOR]

Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single-nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study (SCCS) from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and BMI using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, P = 0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between smoking and weight status in adult women and whether this association differed by race. Methods: The study sample consisted of 22,949 African American and 7831 white women enrolled in the Southern Community Cohort Study from 2002 to 2006. Results: Both African American and white current smokers had decreased odds of being overweight or obese compared to normal-weight nonsmokers, and the inverse trends between current smoking and BMI held for both groups. Conclusion: A strong relationship exists between smoking and weight status, with patterns nearly identical for African Americans and white women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To investigate the role of physical activity, energy balance, and inflammation on the risk of incident sporadic colorectal adenoma, the authors conducted a community- and colonoscopy-based case-control study (n = 177 cases, n = 228 controls) in Winston-Salem and Charlotte, North Carolina, from 1995 to 1997. Participants reported energy intake by a semiquantitative food frequency questionnaire, daily physical activity levels by a standardized questionnaire, and anthropometrics by self-assessment. The odds ratios for adenomas comparing the highest and lowest quantiles of exposure were 0.63 (95% confidence interval (CI): 0.34, 1.17) for physical activity, 0.80 (95% CI: 0.37, 1.73) for total energy intake, 0.70 (95% CI: 0.37, 1.34) for body mass index, 1.46 (95% CI: 0.73, 2.92) for waist/hip ratio, and 2.40 (95% CI: 1.24, 4.63) for height. For the combined effects of these factors, risk was particularly low for those with higher physical activity and low waist/hip ratio (odds ratio = 0.37, 95% CI: 0.18, 0.75) or shorter stature (odds ratio = 0.32, 95% CI: 0.16, 0.62). The inverse effect of physical activity was apparent only among those not taking nonsteroidal antiinflammatory drugs (odds ratio = 0.49, 95% CI: 0.25, 0.94). These findings add further evidence that physical activity and overall patterns indicating positive energy balance increase the risk of adenoma. Furthermore, the results suggest indirectly that biologic mechanisms related to inflammation may play a role in the beneficial effect of physical activity on the risk of incident adenoma. [ABSTRACT FROM AUTHOR]

Background: Limited evidence suggests that adiposity and lack of physical activity may increase the risk of chronic obstructive pulmonary disease (COPD). We investigated the relation of body size and physical activity with incidence of COPD. Methods: We obtained data on anthropometric measurements and physical activity from 113 279 participants in the National Institutes of Health-AARP Diet and Health Study who reported no diagnosis of COPD at baseline (1995-1996). We estimated associations between these measurements and subsequent diagnosis of COPD between 1996 and 2006, with extensive adjustment for smoking and other potentially confounding variables. Results: Participants reported 3648 new COPD diagnoses during follow-up. The incidence of COPD was higher in both severely obese (body mass index [BMI] ≥ 35) and underweight (BMI < 18.5) participants, but after adjustment for waist circumference, only underweight remained positively associated with COPD (relative risk [RR] 1.56, 95% confidence interval [Cl] 1.15-2.11). Larger waist circumference (highest v. normal categories, adjusted RR 1.72, 95% Cl 1.37-2.16) and higher waist-hip ratio (highest v. normal categories, adjusted RR 1.46, 95% Cl 1.23-1.73) were also positively associated with COPD. In contrast, hip circumference (highest v. normal categories, adjusted RR 0.78, 95% Cl 0.62-0.98) and physical activity (≥ 5 v. 0 times/wk, adjusted RR 0.71, 95% Cl 0.63-0.79) were inversely associated with COPD. Interpretation: Obesity, in particular abdominal adiposity, was associated with an increased risk of COPD, and increased hip circumference and physical activity were associated with a decreased risk of COPD. These findings suggest that following guidelines for a healthy body weight, body shape and physical activity decrease the risk of COPD. [ABSTRACT FROM AUTHOR]

Introduction:Body mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA). Methods:Self-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI) Results:During 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR>5 times/week vs. never=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15–18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR5–6 hrs/day vs. <1 hr=0.57, 95%CI: 0.36, 0.92). There was no evidence that BMI was a confounder or effect modifier of any relationship. After adjustment for multiple testing, none of these results were deemed to be statistically significant at p<0.05. Conclusions:We find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior. [ABSTRACT FROM AUTHOR]

The relationship between racial/ethnic residential segregation and physical activity (PA) remains unclear with both positive and negative associations between segregation and PA recently reported. We aimed to examine the relationship between county-level residential segregation and total daily PA and domain-specific PA and whether these associations varied by gender. Participants (N = 2625, mean age [SD] = 45.2 [15.4]) were recruited from the AmeriSpeak panel who completed up to two Activities Completed over Time in 24 Hours (ACT24) previous day recalls in 2019. PA outcomes were created for the following: (1) light PA (LPA), (2) moderate-to-vigorous PA (MVPA), (3) total active time, and (4) domain-specific PA, including leisure, work, household, transport, personal, and other activities. County-level residential segregation based on isolation. Weighted generalized linear models were used to examine the relationship between county-level segregation and each PA outcome, controlling for age, gender, race/ethnicity, income, employment, body mass index, county-level poverty, and census region. Overall, results showed no association between county-level residential segregation and LPA, MVPA, total active time, and domain-specific PA among NH Black and Hispanic populations. Among NH Black females, greater residential segregation was associated with more total hours/day of activity (β = 3.54, 95% CI [0.23, 6.85]). Only NH Black females living in segregated neighborhoods had more total active time. Additionally, it is important to acknowledge that these relationships may vary among NH Black and Hispanic populations. Future studies should examine the interaction between segregation and a broader range of individual, contextual, and environmental factors in relation to PA and domain-specific PA. [ABSTRACT FROM AUTHOR]

Accumulating more steps/day is associated with a lower risk of cancer mortality and composite cancer outcomes. However, less is known about the relationship of steps/day with the risk of multiple site-specific cancers. This study included >22,000 women from the Women's Health Accelerometry Collaboration Cohort (2011−2022), comprised of women from the Women's Health Study and Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study. Steps/day and step intensity were collected with accelerometry. Incident cancer cases and deaths were adjudicated. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of steps/day and step intensity with incident breast, colon, endometrial, lung, and ovarian cancers, a composite of 13 physical activity-related cancers, total invasive cancer, and fatal cancer. On average, women were 73.4 years old, accumulated 4993 steps/day, and had 7.9 years of follow-up. There were small nonsignificant inverse associations with the risks of colon cancer (HR = 0.94, 95% CI: 0.83, 1.05), endometrial cancer (HR = 0.91, 95% CI: 0.82, 1.01), and fatal cancer (HR = 0.95 95% CI: 0.90, 1.00) per 1000 steps/day. More minutes at ≥40 steps/min and a faster peak 10- and 30-min step cadence were associated with a lower risk of endometrial cancer, but findings were attenuated after adjustment for body mass index and steps/day. Among women 62–97 years, there were small nonsignificant inverse associations of colon, endometrial, and fatal cancer with more steps/day. Epidemiologic studies with longer follow-up and updated assessments are needed to further explore these associations. • Less is known about the association of steps/day with site-specific cancers. • Among >22,000 women, 62 to 97 years, the average steps/day was 4993. • Steps/day had weak inverse associations with colon, endometrial, and fatal cancer. • More research is needed on the relationship of steps/day and cancer risk. [ABSTRACT FROM AUTHOR]