Excess Fatness Research Articles

Body fatness across the adult life course and ovarian cancer risk.

Excess body fatness in late adulthood has been observed to increase ovarian cancer risk, but the association is relatively weak. Body fatness can change over time, and timing may differently influence risk. We used a life course epidemiology approach to identify whether the relation between body fatness and ovarian cancer risk is best described by a critical period, accumulation or sensitive period hypothesis. In a population-based case-control study of ovarian cancer in Montreal, Canada (2011-16), data on body mass index (BMI) at each decade starting at age 20 was available. Among 363 cases and 707 controls aged ≥ 50 years, we used a Bayesian relevant life course exposure model to estimate the relative importance of BMI for three pre-specified periods across the adult life course, i.e., early childbearing years, late childbearing years, and peri/postmenopause, on ovarian cancer risk. The accumulation hypothesis best described BMI in relation to ovarian cancer overall, with an odds ratio (OR) for the lifetime effect of BMI (per 5kg/m2 increase) of 1.10 (95% credible interval [CrI]: 0.90-1.35). For invasive ovarian cancer, the OR (95% CrI) for the lifetime effect was 1.16 (0.92-1.48), with BMI during early childbearing years showing the highest relative importance, suggesting this may be a sensitive period. For borderline cancer, the lifetime effect OR was not strongly supportive of an association (OR: 0.90, 95% CrI: 0.53-1.32). The results suggest that a sensitive period of early childbearing years is a candidate hypothesis for further investigation.

Resting metabolic rate is increased after a series of whole body vibration in young men

Resting metabolic rate (RMR) is the largest component of total energy expenditure and increasing it can be of great importance in reducing excess body fatness. Whole body vibration (WBV) can affect energy expenditure during single session of WBV, but the effects of repeated WBV on resting metabolic rate have not been reported. The purpose of this study was to investigate whether a series of WBV would increase resting metabolism in young men. Thirty-two healthy men aged of 21–23 were recruited and randomly assigned to two 16-member groups: a group participating in the WBV intervention and a group without the intervention. The intervention lasted 2 weeks and WBV was performed 5 times a week. Diet, physical activity, body composition and resting metabolic rate were analyzed in the participants. In WBV group significantly increased resting oxygen uptake (p = 0.049) and consequently RMR (p = 0.035) after the intervention. Similar changes were not observed in the control group. This indicates that applied type of vibration in this study can be an addition to obesity therapy, in which, WBV can, among other beneficial metabolic effects, increase RMR and thus total energy expenditure.

Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition.

Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women. These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk.

The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two weight assessments. The association with overall mortality and BC-specific mortality were based on a multivariable Cox and Fine and Gray models, respectively. We performed Mendelian randomization (MR) analysis to investigate the potential causal association. Five-unit higher BMI prediagnosis was associated with a 10% (95% confidence interval: 5–15%) increase in overall mortality and 7% (0–15%) increase in dying from BC. Women with abdominal obesity demonstrated a 23% (11–37%) increase in overall mortality, independent of the association of BMI. Results related to weight change postdiagnosis suggested a U-shaped relationship with BC-specific mortality, with higher risk associated with losing weight or gaining > 2% of the weight annually. MR analyses were consistent with the identified associations. Our results support the detrimental association of excess body fatness on the survival of women with BC. Substantial weight changes postdiagnosis may be associated with poorer survival.

Sugar- and Artificially-Sweetened Beverages and Cancer Mortality in a Large U.S. Prospective Cohort

ObjectivesConsumption of sugar-sweetened beverages (SSB) may be related to risk of cancer mortality independent of, or indirectly through, its established association with increased body mass, but evidence is inconsistent. We evaluated the association of both SSBs and artificially-sweetened beverages (ASB) with mortality from all cancers combined, BMI-related cancers combined, and 22 individual cancers, with and without adjustment for BMI, among U.S. men and women. MethodsIn 1982,934,777 cancer-free participants in the Cancer Prevention Study-II cohort completed questionnaires including information on usual SSB and ASB consumption. Causes of death were identified through 2016. Multivariable Cox proportional hazards regression models were used to examine associations of both beverage types with cancer mortality. ResultsDuring follow-up, 135,093 CPS-II participants died from cancer. Consumption of ≥2 SSB drinks/day vs never was associated with obesity-related cancers combined (HR = 1.05, 95% CI 1.01–1.08, ptrend = 0.057), which became null when BMI was included in statistical models. SSBs were associated with increased risks of colorectal (HR = 1.09, 95% CI, 1.02–1.17, ptrend = 0.011), and kidney (HR = 1.17, 95% CI 1.03–1.34, ptrend = 0.06) cancer mortality, even after BMI adjustment, although for kidney cancer the association remained statistically significant only in continuous models. A positive association of ASB consumption with risk of obesity-related cancers combined (HR = 1.05, 95% CI 1.01–1.08, ptrend = .001) became null after controlling for BMI; however, an increased risk of pancreatic cancer remained after BMI adjustment (HR = 1.16, 95% CI 1.07–1.26, ptrend < 0.0001). ConclusionsSSB consumption may increase risk of obesity-related cancers indirectly through excess body fatness, and of colorectal and kidney cancer mortality independent of obesity. Increased risk of obesity-related cancers with greater ASB intake prior to adjustment for body fatness may reflect confounding by BMI, as ASBs are not considered convincingly related to weight gain. An association of ASB consumption and increased risk of pancreatic cancer deserves further study. Funding SourcesThe American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort.

Excess Body Fatness during Early to Mid-Adulthood and Survival from Colorectal and Breast Cancer: A Pooled Analysis of Five International Cohort Studies.

Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries. Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis. We found a significant dose-response relationship (P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer. Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer. Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.

The association of obesity with thyroid carcinoma risk.

BackgroundThe prevalence of obesity and an increased incidence of thyroid carcinoma (TC) threaten public health in parallel on a global scale. Sufficient evidence supports excess body fatness in thyroid carcinogenesis, and the role and anthropometric markers of obesity have been causally associated with the rising risk of TC.MethodsA literature search was conducted in PubMed. Studies focused on the effect of obesity in TC.ResultsThis review mainly discusses the global incidence and prevalence of obesity‐related TC. We also review the role of obesity in TC and potential clinical strategies for obesity‐related TC.ConclusionsExcess body fatness in early life and TC survival initiate adverse effects later in life.

76 Cattle Production’s Response to Packing Capacity Disruption

In August 2019, a fire at Tyson’s Finney County, Kansas, beef plant removed approximately 5% of U.S. beef packing capacity for 3 months. Subsequent COVID-19 pandemic-related precautions and workforce illness caused multiple packing plants across the country to decrease or stop production in the spring of 2020. Both events resulted in feedlots being unable to ship cattle at optimal finish points or according to projection. Estimates of the number of cattle backlogged during 2020 approach 1 million. Producers were faced with decisions on how to manage finished animals that could not be shipped while considering economic, animal welfare, and animal health outcomes. Many factors further complicated the situation including highly volatile markets, the possibility employee quarantine due to personal or family illness would cause operations to be under-staffed, and shortage of available pens for new cattle. Feeders had the option to slow the rate of growth of finished cattle due to the ability of ruminant animals to utilize low-energy feedstuffs or by calculating programmed rates of gain using the net energy system. Instead, many producers chose to attempt maximal rates of gain hoping persistent growth and feeding margins would offset discounts due to heavy carcass weights and excess fatness when the supply chain began moving again. Regarding new placements, the structure of the beef industry is uniquely developed to absorb cattle in stocker and backgrounding operations. This presentation will review the factors impacting cattle production and provide case-studies related to feeding at maintenance and growth rates, efficiencies, and carcass outcomes of held cattle from an operation and industry level.

The effect of body fatness on regional brain imaging markers and cognitive function in healthy elderly mediated by impaired glucose metabolism

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (β = −0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to −0.006), frontal (β = −0.029; BC 95% CI = −0.063 to −0.005) and temporal (β = −0.022; BC 95% CI = −0.051 to −0.004) lobe cortical thickness, and hippocampal volume (β = −0.029; BC 95% CI = −0.058 to −0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (β = −0.005; BC 95% CI = −0.012 to −0.001/β = −0.005; BC 95% CI = −0.013 to −0.001) and delayed recall for visual information (β = −0.005; BC 95% CI = −0.013 to −0.001/β = −0.005; BC 95% CI = −0.013 to −0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (β = −0.005; BC 95% CI = −0.012 to −0.001), delayed recall for visual information (β = −0.005; BC 95% CI = −0.012 to −0.001), and verbal learning (β = −0.008; BC 95% CI = −0.017 to −0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease.

Steps expressed relative to body fat mass predicts body composition and cardiometabolic risk in adults eating ad libitum.

Excess body fatness is a consequence of a chronic energy surplus (energy intake is greater than energy expenditure). Given the serious health consequences of excess body fatness, factors that influence energy balance and body composition are increasingly important to understand. A total of 34 adults between the ages of 19-40 years made a laboratory visit in which height, weight, body composition, and cardiometabolic risk (CMR) factors were quantified. Participants wore accelerometers for 21-28 days, then returned to the laboratory for a second body composition assessment. Changes in weight and body composition were used to quantify energy balance, and data derived from accelerometers provided markers of physical activity (PA) and sedentariness. Of the markers of PA that we measured, daily step counts expressed relative to fat mass was most strongly and consistently associated with body fatness and CMR status. Step counts expressed relative to fat mass were strongly associated with body composition and CMR in adults eating ad libitum. Longitudinal interventional studies are necessary to determine the efficacy of step count prescriptions expressed relative to existing and target body fatness and CMR levels for improving weight management and metabolic outcomes.

Joint associations of physical activity and body mass index with the risk of established excess body fatness-related cancers among postmenopausal women.

Excess body fatness and physical activity independently influence the risk of several types of cancer. However, few studies have examined whether physical activity mitigates the excess risk associated with higher body mass index (BMI). We examined the individual and joint associations between BMI (kg/m2) and leisure-time moderate-to-vigorous physical activity (MVPA, MET-hours/week) with the risk of three established excess body fatness-related cancers (breast, colon, and endometrial) among 43,795 postmenopausal women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort (1992/1993-2015). Further exclusions for women without an intact uterus resulted in 31,805 women for endometrial cancer analyses. Multivariable Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CIs) with interaction terms to assess multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction. BMI and MVPA were individually associated with breast and endometrial cancer risk, but only BMI was associated with colon cancer risk. In joint analyses, increasing levels of MVPA did not lower the risk of these cancers among obese women. For example, compared to the common referent (BMI 18.5- < 25kg/m2, MVPA > 0- < 7.5 MET-hours/week), BMI ≥ 30kg/m2 was associated with a higher risk of breast cancer among women with low MVPA (> 0-< 7.5 MET-hours/week: HR = 1.42, 95% CI: 1.22 - 1.67) and high MVPA (≥ 15 MET-hours/week: HR = 1.53, 95% CI: 1.25 - 1.87; RERI = 0.20, 95% CI: -0.14, 0.54, multiplicative Pinteraction = 0.64). Our results do not support the hypothesis that leisure-time physical activity mitigates the excess risk associated with higher BMI for risk of breast, endometrial, or colon cancer among postmenopausal women.

Theoretical prediction of life expectancy using lifestyle factors in the EPIC-Heidelberg cohort

Abstract Background The past few decades have witnessed a substantial increase in life expectancy in Western countries, leading to an increase in the prevalence of age-related chronic diseases. Several lifestyle risk factors (i.e. smoking, adiposity, unhealthy diet, heavy alcohol drinking and lack of physical activity) have been responsible for a large proportion of premature deaths, as they can affect the incidence of age-related chronic diseases. Our objective was to predict the loss of residual life expectancy (RLE) associated with these lifestyle factors, using data from the EPIC-Heidelberg cohort, linked to an up-to-date mortality registry. Methods A total of 23,324 German adults, aged 40 years and above were included (1994-1998) and followed until June 2019. A multi-adjusted parametric proportional hazard model (Gompertz hazard distribution), used to predict survival probabilities, followed by a life table approach was used. Results At age 40, being a heavy smoker (&amp;gt; 10 cigarettes/day) was associated with 10.5 y loss of RLE in men and 8.3 in women. Low body mass index (&amp;lt; 22.5 kg/m2) was associated with a RLE loss of 3.7 y in men and 1.4 y in women, while obesity was associated with 4.4 y in men and 3.8 y in women. Heavy alcohol drinking (&amp;gt; 4 drinks/day) was associated with a loss of 4.5 y in men, and high red/processed meat consumption (≥ 120 g/day) was associated with a loss of 1.1y in men and 2.1 y in women. Compared with an overall healthy lifestyle, combined unhealthy behaviors were associated with a loss of RLE of 21.4 y in men and 15.5 y in women. Conclusions Prevention strategies encouraging the adoption of an overall healthy lifestyle, particularly by avoiding smoking, heavy alcohol drinking, excess body fatness and reducing red/processed meat consumption, help reducing premature deaths. An extension of this project using blood biomarkers measures is ongoing. Key messages Adopting a healthy lifestyle by avoiding or reducing the exposure to risk factors might contribute to a longer life expectancy. Tobacco use, adiposity, and alcohol are probably the main modifiable lifestyle factors affecting life expectancy.

Body Composition Using Air Displacement Plethysmography in Children With Inflammatory Bowel Disease.

The aim of the study was to assess the body composition of children with inflammatory bowel disease (IBD) and to study the accuracy of clinically available tools in predicting excess body fatness. We aimed at also exploring the influence of adiposity on pharmacokinetics during early Infliximab exposure. Prospective cohort study in 5- to 17-year-old children with IBD initiating Infliximab therapy. Patient demographic, phenotypic, and laboratory data at the time of Infliximab initiation were recorded. Body composition was assessed using air displacement plethysmography (ADP). fat mass index (FMI = fat mass [kg]/(height [m])) was calculated to determine excess adiposity (defined as FMI ≥75th centile). Anthropometrics (weight, height, mid upper arm circumference [MUAC] and triceps skin fold thickness [TSF]) were obtained and MUAC and TSF measurements were used to calculate arm fat area (AFA) and arm muscle area z-scores. Statistical analysis was applied as appropriate. Fifty-three (68% male; 55% Crohn disease [CD], 45% ulcerative colitis [UC], median [IQR] age 15 [13-16] years) children with IBD were included. Twenty-four percentage of children with IBD (21% CD, 29% UC) had excess adiposity. Four children (31%) with FMI ≥75th centile were not identified by body mass index (BMI) alone (kappa of 0.60), and 2 children (15%) were not identified by AFA z-score alone. The intra- and interobserver reliability of MUAC and TSFT measurements was excellent. There was no difference in Infliximab trough levels at the end of induction between those with FMI less than or ≥75th centile. Excess adiposity affects approximately 1 in 4 young patients with IBD and can be missed by routine obesity screening. Our exploratory study did not raise concerns of underexposure to infliximab in those children with excess adiposity during early drug exposure.

The food frequency intake and eating behaviours of metabolically obese and non obese polycystic ovary syndrome women

AbstractIntroduction: Normal weight obesity is characterized as regular BMI and excessive body fatness. This type of metabolic obesity may be observed and overlooked in polycystic ovary syndrome women (PCOS), in whom obesity and increased cardiometabolic risk are observed. There are limited data concerning eating habits and lifestyle behaviours of/in normal weight obesity PCOS women. The purpose of this study is to distinguish the food frequency intake and eating habits behaviours of PCOS women characterized by regular weight and body fatness, regular weight and excess fatness and overweight and excess body fatness.Methods: Women with PCOS (n = 149, BMI: 26 ± 6 kg/m2, aged 17–44 years) were divided into three groups according to the BMI and body fatness percentage (FM%): Regular weight and FM% (RW, n = 64), regular weight and high FM% (RWHF, n = 24) and high weight and high FM% (HWHF, n = 61). FM% was measured by air displacement plethysmography (BodPod, Life Measurement Inc, Concord, CA). Anthropometrics included weight, height and waist-to-hip-ratio (WHR) were measured. Food frequency intake and lifestyle behaviours were assessed by Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN, The Committee of Human Nutrition, Polish Academy of Science). To assess psychological factors influencing nutrition, My Eating Habits (MEH) Questionnaire was used. To detect the differences between the groups Kruskall-Wallis ANOVA and Mann Whitney-U tests were used.Results: The results showed that the groups with higher body fatness (HWHF and RWHF) had significantly higher scores of dietary restrictions than the RW group. The RWHF group had significantly lower frequency intake of grains and lower physical activity in relation to other groups. In the group HWHF we indicated the higher risk of eating disorders since scored there higher in emotional overeating section of Eating Habits questionnaire.Conclusion:The differences in body fatness in PCOS women might by driven by eating behaviours and frequency of intake selected food groups. Individual approach emphasized on dietary coaching of eating and lifestyle habits, might be beneficial to body composition management and cardiometabolic risk reduction in PCOS women.

Age period cohort analysis in cancers associated with overweight and obesity in Ireland

AbstractThe Central Statistics Office (CSO) in Ireland report that 62% of adults were overweight or obese in 2017(1). In 2019, the latest data from the national longitudinal study “Growing Up in Ireland” showed that 15% of five-year olds were overweight and 5% were obese(2). According to WHO projections, Ireland may have the highest prevalence of overweight and obesity in Europe by 2030(3). The International Agency for Research on Cancer (IARC) state there is sufficient evidence for a cancer preventative effect of the absence of excess body fatness for 13 different cancer sites(4). Recent USA based research showed that the risk of developing an obesity-related cancer seems to be increasing in a stepwise manner in successively younger birth cohorts(5), therefore we aimed to investigate trends in the age of obesity related cancer diagnosis.National Cancer Registry Ireland (NCRI) data was obtained for 25 to 84 year olds between 1997 and 2016 for several cancer types and 5-year intervals were constructed to categorise age (25–29, 30–34 etc.) and year of diagnosis (1997–2001, 2002–2006 etc.). An age-period-cohort model was fitted to each cancer type, resulting in estimated temporal trends in incidence (expressed as annual percent change (APC) per year) and significance of the trend across age groups was tested using a Wald test(5).Analysis of NCRI data reflect significantly increasing incidence of colorectal cancer with decreasing age in Ireland (n = 40703, p = 0.00). Despite the limitation of low numbers for several cancer sites in younger age groups, similar trends were observed for a number of cancer types including thyroid and cervical cancer (p &lt; 0.05). Although other factors (such as early detection) may contribute to these observations, addressing the large increase in incidence of obesity and colorectal cancer among young adults is essential. Research to identify exposure to modifiable risk factors, including nutrition and physical activity, throughout life in Ireland is necessary to examine potential determinants of such trends.

Protocol for validating simple measures of body fatness and physical activity of children in twelve African countries: the ROUND-IT Africa study

Body fatness and physical activity (PA) among children should be measured accurately to address the pandemics of obesity and physical inactivity. Limited accurate PA data exist in the African region, and crude proxy measures of body composition (such as body mass index: BMI) and physical activity (such as questionnaires) may have limited most surveys and studies from the region. A stable isotope technique (deuterium dilution) and accelerometry provide ‘gold standards’ for validating measures of body fatness and PA, respectively. The consortium on “Reducing Obesity Using Nuclear Techniques to Design Interventions in Africa (ROUND-IT)” Study, therefore aimed to validate the accuracy of, 1) World Health Organisation’s (WHO) BMI-for-age as a means of assessing excessive body fatness; 2) the Physical Activity Questionnaire for Children (PAQ-C) as a means of measuring PA, and 3) to describe accelerometer-measured PA in a large African multi-country sample of children 6 – 11 years of age (n=2050). ROUND-IT Africa is a cross-sectional multi-centre study conducted in 12 countries (Benin, Ghana, Kenya, Mali, Mauritius, Morocco, Namibia, Senegal, Tunisia, Uganda, the United Republic of Tanzania and South Africa). Data collection began in April 2014 and was completed at the end of 2018. Height, body weight and waist circumference were measured using standard methods. Obesity was defined based on WHO’s BMI-for-age criteria. Body fatness was measured using total body water, and excess fatness determined using the criterion-referenced thresholds of >25% (boys) and >30% (girls). PA and sedentary behavior were assessed for 7 days in randomly assigned subsamples by accelerometry. The study was approved by local ethics committees in each participating country. Findings of the research, which will add to the existing body of scientific knowledge on African children, will be disseminated through journal publications, technical reports, conferences, and contacts with relevant non-governmental organisations, particularly the WHO.Keywords: Children, obesity, overweight, body composition, physical activity.

Abstract LB-179: Pre- and post-diagnosis body mass index, weight change, and prostate cancer-specific mortality among prostate cancer survivors in the US

Abstract Accumulating evidence suggests that excess body fatness is associated with an increased risk of aggressive prostate cancer. However, the roles of body mass index (BMI -kg/m2), reported before and after diagnosis, and weight change in long-term prostate cancer survival remain unclear. Prospective data from men diagnosed with non-metastatic prostate cancer between 1992 and 2013 were obtained from the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort. Weight was self-reported on surveys completed at enrollment into the Nutrition Cohort in 1992, in 1997, and every 2 years thereafter. Pre-diagnosis BMI was from the first survey completed &amp;gt;1 year before diagnosis and post-diagnosis BMI from the first survey completed &amp;gt; 2 years after diagnosis to allow for treatment completion. BMI was classified as ideal (18.5-&amp;lt;25), overweight (25-&amp;lt;30), and obese (30+). Weight change was the difference in weight (lbs.) from pre- to post-diagnosis. Follow-up began on the date of diagnosis in pre-diagnosis analyses (n=9,867) and, to reduce the potential for reserve causation, 4-years after the post-diagnosis survey in post-diagnosis analyses (n=6,860). Follow-up ended at death or December 2014, whichever came first. Cox proportional hazard models were used to estimate cause-specific hazard ratios (HR) and 95% confidence intervals (95% CI), adjusted for age, race, education, initial treatment, stage, Gleason score, node involvement, comorbidities, pre-diagnosis BMI (weight change models only), smoking, alcohol, and physical activity. A total of 614 and 330 prostate cancer deaths occurred in the pre- and post-diagnosis cohorts, respectively. The median follow-up time was 10.6 years (interquartile range (IQR) =7.9) and 5.5 years (IQR=6.1) in the pre- and post-diagnosis cohorts, respectively. In pre-diagnosis multivariable models, BMI was not associated with prostate cancer-specific mortality (e.g., Obese vs Ideal: HR=1.09, 95% CI: 0.83, 1.42). In post-diagnosis models, compared to men with an ideal BMI, the hazard of prostate cancer-specific death was similar among overweight men (HR=1.08, 95%CI: 0.84, 1.39) and higher among obese men (HR=1.41, 95% CI: 1.02, 1.97). Compared to men who maintained their weight (± 5 lbs.), the hazard of prostate cancer-specific mortality was higher among men who gained &amp;gt; 10 lbs. (HR=1.33, 95%CI: 0.99, 1.77) or lost &amp;gt; 10 lbs. (HR=1.33, 95%CI: 0.92, 1.92), but was similar among men who gained or lost 5-10 lbs. Our results suggest that post-diagnosis obesity and weight gain may be associated with increased risk of prostate cancer-specific mortality. The suggestion of an inverse association between weight loss and higher prostate cancer-specific mortality in our study should be interpreted with caution as it is unknown whether weight loss occurring was intentional or due to advanced disease. Citation Format: Alyssa N. Troeschel, Eric J. Jacobs, W. Dana Flanders, Victoria L. Stevens, Terryl J. Hartman, Lauren E. McCullough, Ted Gansler, Ying Wang. Pre- and post-diagnosis body mass index, weight change, and prostate cancer-specific mortality among prostate cancer survivors in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-179.

Abstract 961: Joint associations of physical activity and body mass index and the risk of excess body fatness-related cancer

Abstract Background: Consistent evidence has linked excess body fatness (EBF), typically measured in large epidemiologic studies using body mass index (BMI), with a higher risk of 13 types of cancer. Whether physical activity mitigates any of the excess risk associated with EBF is unclear—as few studies have examined the joint association between BMI and physical activity. Methods: We examined the joint association of BMI and physical activity on the risk of 12 of the 13 EBF-related cancers (excluding meningioma and including esophagus [adenocarcinoma], gastric cardia, colon and rectum, liver, gallbladder, pancreas, postmenopausal breast, corpus uteri, ovary, kidney [renal cell], thyroid, and multiple myeloma) among 70,658 men and 72,209 postmenopausal women (median age: 63 years) without a history of cancer at study entry in the Cancer Prevention Study II Nutrition Cohort (1992-2013). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the individual and joint associations between BMI (kg/m2) and recreational physical activity (MET-hours/week) at study entry and first cancer incidence. Results: Between 1992-2013, 3,860 men and 9,001 women were diagnosed with an EBF-related cancer. Compared to normal weight (BMI 18.5-&amp;lt;25 kg/m2), overweight (25-&amp;lt;30 kg/m2) was associated with a modest increased risk of EBF-related cancer (men: HR 1.12; 95% CI: 1.04, 1.21; women: HR 1.13; 95% CI: 1.08, 1.19) and obesity (≥30 kg/m2) with a stronger risk (men: HR 1.48; 95% CI: 1.34, 1.63; women: HR 1.48; 95% CI: 1.40, 1.57). Higher levels of physical activity (&amp;gt;15 vs. &amp;gt;0-&amp;lt;7.5 MET-hrs/wk) were associated with a lower risk for EBF-related cancer among women (HR: 0.90; 95% CI: 0.85-0.95) but less so among men (HR: 0.96; 95% CI: 0.88, 1.04). Among women, there was no evidence of interaction between physical activity and BMI for the risk of EBF-related cancer (P-interaction=0.59); however, there was suggestive evidence that the excess risk associated with overweight was modestly mitigated by the highest level of physical activity (HR: 1.00; 95% CI: 0.91, 1.10). Among men, there was some evidence of an interaction between BMI and physical activity on risk (P-interaction=0.06) with the higher risk associated with overweight limited to those who were inactive (HR: 1.27; 95% CI: 1.08, 1.49). However, risk was higher for obese men irrespective of physical activity level. Conclusion: Our results suggest that higher levels of recreational physical activity may offset a small amount of the increased risk of EBF-related cancer among overweight men and women. However, physical activity does not appear to mitigate the strong effect of obesity (BMI ≥30 kg/m2) on risk of EBF-related cancers, thus reinforcing the importance of maintaining a healthy body weight even if physically active. Citation Format: Maret L. Maliniak, Susan M. Gapstur, Lauren E. McCullough, Erika Rees-Punia, Mia M. Gaudet, Caroline Y. Um, Mark A. Guinter, Elizabeth A. Fallon, Alpa V. Patel. Joint associations of physical activity and body mass index and the risk of excess body fatness-related cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 961.

Type 2 Diabetes, Body Mass Index and Cancer Mortality: A Population-Based Matched Cohort Study of 1.0 Million Adults in England

Background: Individuals with type 2 diabetes (T2D) have higher cancer mortality than individuals without T2D. The underlying mechanisms are likely to be multi-factorial, but the mutual risk factor of excess body fatness (commonly approximated by body mass index, BMI) is thought to be important. We first tested the hypothesis that excess cancer deaths in T2D are mainly from obesity-related cancers (ORCs); and second, that increasing BMI among individuals with T2D is positively associated with ORC mortality. Methods: We conducted a matched cohort study in the Clinical Practice Research Datalink in England, linked with mortality statistics (1998-2015), and derived cohorts with incident T2D (176,886) versus never diabetes (control: 852,946), aged 30 to 85 years. Among individuals with T2D, we calculated peri-diagnosis (± 12 months date of T2D diagnosis) BMI. The primary outcome was risk for total cancer mortality, categorised into deaths from obesity-related (ORC: 13 cancer types) and non-ORC. Secondary outcomes were all-cause and cardiovascular disease (CVD) mortalities. We used Cox models with multiple imputations and estimated hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes. We tested for several sources of bias, including accounting for cross-BMI category age differences; reverse causality; alternate time BMI determinations (for example, at 4 to 6 years prior to T2D diagnosis); and competing risks of death. Results: With a mean follow-up of 7.1 years, there were 47,459 cancer deaths (T2D: 9606; non-T2D: 37,853). Compared with the control population, T2D was associated with higher ORC mortality in men (HR: 1.708, 95% CIs: 1.564-2.865) and women (HR: 1.338 95% CIs: 1.240-1.444). Unexpectedly, there was an increase in deaths from non-ORC in women (HR: 1.185, 1.008-1.169), but not men. Among individuals with T2D, overall, associations were generally null or inverse, except for positive associations in specific cancers, such as endometrial (HR per 5 kg/m2: 1.416 95% CIs: 1.252-1.601) and ovarian (HR per 5 kg/m2: 1.144 95% CIs: 1.018-1.286) cancer mortalities. We found evidence of reverse causality, but no evidence of effect modification by age, associations with prior BMI, or competing risk. Interpretation: Individuals with T2D have higher obesity-related cancer mortality than those without T2D, supporting the notion that obesity is an important mechanism of excess cancer mortality in 2TD. The unexpected modest higher non-obesity-related cancer mortality suggests that factors beyond body fatness might be drivers of excess cancer mortality in 2TD. Funding Statement: This work was supported by CRUK via the funding to Cancer Research UK Manchester Centre: [C147/A18083] and [C147/A25254]. Declaration of Interests: AGR has received lecture honoraria from Merck Serona and Janssen-Cilag, and independent research funding and lecture honoraria from Novo Nordisk and Sanofi Pasteur MSD. DMA has received independent reaserch funding from Abbvie and the Leo Foundation. All other authors declare no competing interests. Ethics Approval Statement: This study is based on data from the Clinical Practice Research Datalink obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data is provided by patients and collected by the NHS as part of their care and support. The study was approved by the independent scientific advisory committee (ISAC) for Clinical Practice Research Datalink research (protocol number: 17_137R).

The Obesity Paradox in Cancer: Epidemiologic Insights and Perspectives.

Controversy exists whether excess body fatness (measured by body mass index (BMI)) is associated with better cancer survival ("obesity paradox"). Here, we review the obesity paradox in cancer research and discuss potential explanations and future research directions. Overweight and obese cancer patients have better survival for diverse cancers. This apparent obesity paradox may be largely explained by methodological limitations including reverse causation, selection bias, confounding, and reliance of BMI as a measure of adiposity in cancer patients. A growing number of studies show promising evidence that precisely quantified body composition can provide important prognostic information in cancer care, such that low muscle and high adiposity are associated with worse clinical outcomes in cancer patients. The term obesity paradox in cancer, implying a causally beneficial role of adiposity, is misleading. Understanding the role of muscle and adiposity may reduce the confusion and inform precision oncology care.