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AimsDisparities persist on the prevalence of undiagnosed type 2 diabetes in racial/ethnic minorities in the USA. This study evaluated the association between BMI and incident type 2 diabetes risk by racial/ethnic group, to determine whether BMI and presence of type 2 diabetes risk factors may help clinicians better target type 2 diabetes screening.MethodsThis prospective cohort analysis included 5659 adults free of type 2 diabetes at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort (2000-2011). BMI was measured at baseline and time-updated at subsequent visits. Incident type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/l, or use of any diabetes medications.ResultsThe mean (sd) age was 62 (10) years and 42% of participants were white, 26% African American, 20% Hispanic and 12% Chinese American. During follow-up, 696 (12%) new type 2 diabetes cases were observed. In age- and sex-adjusted models, in the presence of one or more type 2 diabetes risk factors (the most common scenario), a 10% risk of incident type 2 diabetes was observed at a BMI of 21.7 kg/m2 [95% confidence interval (CI) 20.1 to 22.8] in Chinese Americans, 23.8 kg/m2 (22.7 to 24.9) in Hispanics, 24.7 kg/m2 (23.7 to 25.6) in African Americans and 26.2 kg/m2 (25.1 to 26.9) in white participants.ConclusionsThis study supports including BMI and presence of type 2 diabetes risk factors as action points for clinicians to prioritize which adults aged ≥ 45 years should be screened. The application of race/ethnicity-specific BMI thresholds may reduce the disparity of undiagnosed type 2 diabetes observed in minority groups.

BackgroundSome obese adults are not afflicted by the metabolic abnormalities often associated with obesity (the 'metabolically healthy obese' (MHO)); however, they may be at increased risk of developing cardiometabolic abnormalities in the future. Little is known about the relative incidence of individual components of metabolic syndrome (MetSyn).MethodsWe used data from a multicenter, community-based cohort aged 45-64 years at recruitment (the Atherosclerosis Risk In Communities study) to examine the first appearance of any MetSyn component, excluding waist circumference. Body mass index (BMI, kg m-2) and cardiometabolic data were collected at four triennial visits. Our analysis included 3969 adults who were not underweight and free of the components of MetSyn at the initial visit. Participants were classified as metabolically healthy normal weight (MHNW), overweight (MHOW) and MHO at each visit. Adjusted hazard ratios (HR) and 95% confidence intervals were estimated with proportional hazards regression models.ResultsThe relative rate of developing each risk factor was higher among MHO than MHNW, with the strongest association noted for elevated fasting glucose (MHO vs MHNW, HR: 2.33 (1.77, 3.06)). MHO was also positively associated with elevated triglycerides (HR: 1.63 (1.27, 2.09)), low high-density lipoprotein-cholesterol (HR: 1.68 (1.32, 2.13)) and elevated blood pressure (HR: 1.54 (1.26, 1.88)). A similar, but less pronounced pattern was noted among the MHOW vs MHNW.ConclusionsWe conclude that even among apparently healthy individuals, obesity and overweight are related to more rapid development of at least one cardiometabolic risk factor, and that elevations in blood glucose develop most rapidly.

Purpose: The mechanisms driving the physical activity-breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest. Genetic variation in CAT or antioxidant-related polymorphisms may mediate the physical activity-breast cancer association.Methods: We investigated the main and joint effects of three previously unreported polymorphisms in CAT on breast cancer risk. We also estimated interactions between recreational physical activity (RPA) and 13 polymorphisms in oxidative stress-related genes. Data were from the Long Island Breast Cancer Study Project, with interview and biomarker data available on 1,053 cases and 1,102 controls.Results: Women with ≥1 variant allele in CAT rs4756146 had a 23 % reduced risk of postmenopausal breast cancer compared with women with the common TT genotype (OR = 0.77; 95 % CI = 0.59-0.99). We observed two statistical interactions between RPA and genes in the antioxidant pathway (p = 0.043 and 0.006 for CAT and GSTP1, respectively). Highly active women harboring variant alleles in CAT rs1001179 were at increased risk of breast cancer compared with women with the common CC genotype (OR = 1.61; 95 % CI, 1.06-2.45). Risk reductions were observed among moderately active women carrying variant alleles in GSTP1 compared with women homozygous for the major allele (OR = 0.56; 95 % CI, 0.38-0.84).Conclusions: Breast cancer risk may be jointly influenced by RPA and genes involved in the antioxidant pathway, but our findings require confirmation. [ABSTRACT FROM AUTHOR]

Previous research demonstrates the joint association of self-reported physical activity and genotype with coronary artery disease. However, an existing research gap is whether accelerometer-measured overall physical activity or physical activity intensity can offset genetic predisposition to coronary artery disease. This study explores the independent and joint associations of accelerometer-measured physical activity and genetic predisposition with incident coronary artery disease. Incident coronary artery disease based on hospital inpatient records and death register data serves as the outcome of this study. Polygenic risk score and overall physical activity, measured as Euclidean Norm Minus One, and intensity, measured as minutes per day of moderate-to-vigorous intensity physical activity (MVPA), are examined both linearly and by decile. The UK Biobank population-based cohort recruited over 500,000 individuals aged 40 to 69 between 2006 and 2010, with 103,712 volunteers participating in a weeklong wrist-worn accelerometer study from 2013 to 2015. Individuals of White British ancestry (n = 65,079) meeting the genotyping and accelerometer-based inclusion criteria and with no missing covariates were included in the analytic sample. In the sample of 65,079 individuals, the mean (SD) age was 62.51 (7.76) and 61% were female. During a median follow-up of 6.8 years, 1,382 cases of coronary artery disease developed. At the same genetic risk, physical activity intensity had a hazard ratio (HR) of 0.41 (95% CI: 0.29-0.60) at the 90th compared to 10th percentile, equivalent to 31.68 and 120.96 minutes of moderate-to-vigorous physical activity per day, respectively, versus an HR of 0.61 (95% CI: 0.52-0.72) for overall physical activity. The combination of high genetic risk and low physical activity intensity showed the greatest risk, with an individual at the 10th percentile of genetic risk and 90th percentile of intensity facing an HR of 0.14 (95% CI: 0.09-0.21) compared to an individual at the 90th percentile of genetic risk and 10th percentile of intensity. Physical activity, especially physical activity intensity, is associated with an attenuation of some of the risk of coronary artery disease but this pattern does not vary by genetic risk. This accelerometer-based study provides the clearest evidence to date regarding the joint influence of genetics, overall physical activity, and physical activity intensity on coronary artery disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC)., Methods: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC., Results: The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC., Conclusions: Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Interest in understanding the relationship between body composition and cancer survival has remained strong for decades, with a number of recent systematic reviews on the topic. However, the current state of evidence is based on heterogeneous exposure definitions based on anthropometry, yielding inconsistent findings with regard to this association. Recently the field has taken an exciting direction with the application of radiological assessments to measure specific aspects of body composition, yet reconciliation of findings from these modern assessment tools with those from the historic use of anthropometric data proves challenging. In this paper, I briefly review the biological basis for a link between body composition and cancer survival and summarize the epidemiological evidence with consideration to specific exposure measures. As enthusiasm is building around novel assessments, I conclude with a discussion of issues that researchers should be aware of when interpreting results from these new modalities., (© 2023. The Author(s).)

Importance: Racial and ethnic inequities in the criminal-legal system are an important manifestation of structural racism. However, how these inequities may influence the risk of severe maternal morbidity (SMM) and its persistent racial and ethnic disparities remains underinvestigated., Objective: To examine the association between county-level inequity in jail incarceration rates comparing Black and White individuals and SMM risk in California., Design, Setting, and Participants: This population-based cross-sectional study used state-wide data from California on all live hospital births at 20 weeks of gestation or later from January 1, 1997, to December 31, 2018. Data were obtained from hospital discharge and vital statistics records, which were linked with publicly available county-level data. Data analysis was performed from January 2022 to February 2023., Exposure: Jail incarceration inequity was determined from the ratio of jail incarceration rates of Black individuals to those of White individuals and was categorized as tertile 1 (low), tertile 2 (moderate), tertile 3 (high), with mean cutoffs across all years of 0 to 2.99, 3.00 to 5.22, and greater than 5.22, respectively., Main Outcome and Measures: This study used race- and ethnicity-stratified mixed-effects logistic regression models with birthing people nested within counties and adjusted for individual- and county-level characteristics to estimate the odds of non-blood transfusion SMM (NT SMM) and SMM including blood transfusion-only cases (SMM; as defined by the Centers for Disease Control and Prevention SMM index) associated with tertiles of incarceration inequity., Results: This study included 10 200 692 births (0.4% American Indian or Alaska Native, 13.4% Asian or Pacific Islander, 5.8% Black, 50.8% Hispanic or Latinx, 29.6% White, and 0.1% multiracial or other [individuals who self-identified with ≥2 racial groups and those who self-identified as "other" race or ethnicity]). In fully adjusted models, residing in counties with high jail incarceration inequity (tertile 3) was associated with higher odds of SMM for Black (odds ratio [OR], 1.14; 95% CI, 1.01-1.29 for NT SMM; OR, 1.20, 95% CI, 1.01-1.42 for SMM), Hispanic or Latinx (OR, 1.24; 95% CI, 1.14-1.34 for NT SMM; OR, 1.20; 95% CI, 1.14-1.27 for SMM), and White (OR, 1.02; 95% CI, 0.93-1.12 for NT SMM; OR, 1.09; 95% CI, 1.02-1.17 for SMM) birthing people, compared with residing in counties with low inequity (tertile 1)., Conclusions and Relevance: The findings of this study highlight the adverse maternal health consequences of structural racism manifesting via the criminal-legal system and underscore the need for community-based alternatives to inequitable punitive practices.

Over two-thirds of pregnant women in the U.S. have insufficient 25(OH)D (Vitamin D) concentrations, which can adversely impact fetal health. Several pollutants have been associated with 25(OH)D, but have not been considered in the context of chemical co-exposures. We aimed to determine associations between a broad mixture of prenatal environmental chemical exposures and 25(OH)D concentrations in mid-pregnancy. Stored mid-pregnancy serum samples were assayed from 421 women delivering live births in Southern California in 2000-2003. 25(OH)D, six BFRs, eleven polychlorinated biphenyls (PCBs), six per- and polyfluoroalkyl substances, and two organochlorine pesticides were detected in ≥60% of specimens. Gestational exposures to airborne particulate matter ≤ 10 μm (PM 10 ) and ≤ 2.5 μm (PM 2.5 ), nitrogen monoxide (NO), nitrogen dioxide (NO 2 ), and ozone concentrations were derived from monitoring station data. Bayesian Hierarchical Modeling (BHM) and Bayesian Kernel Machine Regression (BKMR) analyses estimated overall mixture and individual chemical associations accounting for co-exposures and covariates with mean 25(OH)D levels, and BHM was used to estimate associations with insufficient (<75 nMol/L) 25(OH)D levels. Non-mixture associations for each chemical were estimated with linear and logistic models. PM 10 [BHM estimate: -0.133 nmol/l 95% Credible Interval (-0.240, -0.026)] was associated with lower 25(OH)D in BHM and BKMR. Higher quantiles of combined exposures were associated with lower 25(OH)D, though with wide credible intervals. In non-mixture models, PM 10 , PM 2.5 , NO, and NO 2 were associated with lower concentrations, while O 3 and PBDE153 were associated with higher 25(OH)D and/or lower insufficiency. While some chemicals were associated with increased and others with decreased 25(OH)D concentrations, the overall mixture was associated with lower concentrations. Mixture analyses differed from non-mixture regressions, highlighting the importance of mixtures approaches for estimating real-world associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited., Methods: This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated., Results: Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced., Conclusions: Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors., Impact: We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors., (©2023 American Association for Cancer Research.)

Purpose: Adverse childhood experiences (ACEs) are associated with poor adulthood health. Multiracial people have elevated mean ACEs scores and risk of several outcomes. We aimed to determine whether this group should be targeted for prevention efforts., Methods: We analyzed three waves (1994-2009) of the National Longitudinal Study of Adolescent to Adult Health (n = 12,372) in 2023, estimating associations between four or more ACEs and physical (metabolic syndrome, hypertension, asthma), mental (anxiety, depression), and behavioral (suicidal ideation, drug use) outcomes. We estimated adjusted risk ratios for each outcome in modified Poisson models interacting race and ACEs. We used the interaction contrast to estimate race-specific excess cases per 1000 relative to Multiracial participants., Results: Excess case estimates of asthma were smaller for White (-123 cases, 95% CI: -251, -4), Black (-141, 95% CI: -285, -6), and Asian (-169, 95% CI: -334, -7) participants compared to Multiracial participants. Black (-100, 95% CI: -189, -10), Asian (-163, 95% CI: -247, -79) and Indigenous (-144, 95% CI: -252, -42) participants had fewer excess cases of and weaker relative scale association with anxiety compared to Multiracial participants., Conclusions: Adjusted associations with asthma and anxiety appear stronger for Multiracial people. Existing ACEs prevention strategies should be tailored to support Multiracial youth and families., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Lifestyle habits can impact breast cancer development, but its impact on breast cancer prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive breast cancer enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005-2013) and the 2-year follow-up., Methods: We calculated a post-diagnosis lifestyle score (range, 0-18) based on 9 diet, physical activity, and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences)., Results: The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM; HR per 2-point increase = 0.90; 95% CI, 0.82-0.98), and breast cancer-related mortality (HR, 0.79; 95% CI, 0.67-0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR, 0.61, 95% CI, 0.37-1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA, 0.52; 95% CI, 0.35-0.78)., Conclusions: Results suggest that women with breast cancer may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines., Impact: This information may potentially guide lifestyle recommendations for breast cancer survivors to reduce mortality risk., (©2023 American Association for Cancer Research.)

Objective: This study examined the association of adolescent BMI trajectory with adult metabolic syndrome (MetSyn) and with intergenerational obesity., Methods: This study used data from the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (1987-1997). Data from the 20-year follow-up (2016-2019) study were included from the original participants (N = 624) and their children (N = 645). Adolescent BMI trajectories were identified using latent trajectory modeling. Mediation analysis using logistic regression models was performed to estimate confounder-adjusted odds ratios (OR) and 95% CI between adolescent BMI trajectory and adult MetSyn. Using similar methods, the association between BMI trajectory and offspring obesity was examined., Results: Latent trajectory modeling identified four patterns: "weight loss then gain" (N = 62); "persistently normal" (N = 374); "persistently high BMI" (N = 127); and "weight gain then loss" (N = 61). Women who had a persistently high BMI trajectory had twice the odds of having children who met the definition for obesity compared with the persistently normal group, adjusting for adult BMI (OR: 2.76; 95% CI: 1.39-5.46). None of the trajectory groups was associated with adult MetSyn compared with the persistently normal group., Conclusions: Intermittent adolescent obesity may not confer MetSyn risk during adulthood. However, maternal adolescent BMI trajectories that are persistently high may increase the odds of intergenerational obesity among offspring., (© 2023 The Obesity Society.)

A greater risk of cardiovascular disease is associated with low educational attainment and high adiposity. Despite the correlation between low educational attainment and high adiposity, whether educational attainment modifies the risk of CVD caused by high adiposity remains poorly understood. We investigated the effect of adiposity (body mass index [BMI] and waist-to-hip ratio adjusted for BMI [WHRadjBMI]) on incident CVD among individuals with varying education levels, using associational and one-sample Mendelian randomization (MR) survival analyses. Data were collected from 2006 to 2021, and sample sizes were 254,281 (27,511 CVD cases) for BMI and 253,968 (27,458 CVD cases) for WHRadjBMI. In the associational model, a standard deviation (SD) higher BMI was associated with 19.81 (95% CI: 18.55-21.06) additional cases of incident CVD per 10,000 person-years for individuals with a secondary education, versus 32.96 (95% CI: 28.75-37.17) for those without. When university degree served as the education variable, education group differences attenuated, with 18.26 (95% CI: 16.37-20.15) cases from a one SD higher BMI for those with a university degree versus 23.18 [95% CI: 21.56-24.72] for those without. For the MR model, an SD higher BMI resulted in 11.75 (95% CI: -0.84-24.38) and 29.79 (95% CI: 17.20-42.44) additional cases of incident CVD per 10,000 person-years for individuals with versus without a university degree. WHRadjBMI exhibited no effect differences by education. While the associational model showed evidence of educational attainment modifying the relationship between adiposity and incident CVD, it does not modify the association between adiposity and incident CVD in the MR models. This suggests either less education does not cause greater risk of incident CVD from high adiposity, or MR models cannot detect the effect difference. The associational point estimates exist within the MR models' confidence intervals in all BMI analyses, so we cannot rule out the effect sizes in the associational models., Competing Interests: None declared., (© 2023 The Authors.)

Background: Prenatal pesticide exposure has been associated with poorer neurodevelopment during childhood, which could lead to greater risk-taking behaviors and delinquency in adolescence. This association may be augmented by adversity exposure., Objectives: Evaluate the relationship between prenatal pesticide exposure and risk-taking behavior in young adults at 18-years of age. Assess whether adversity exposure modifies these associations., Methods: Participants included mother-child dyads (n = 467) enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study, a longitudinal birth cohort set in the agricultural Salinas Valley of California. We estimated agricultural pesticide use within one km of maternal residences during pregnancy using a geographic information system, residential addresses, and California's Pesticide Use Reporting data. We used Bayesian hierarchical regression to evaluate associations of prenatal exposure to a mixture of 11 neurotoxic pesticides with self-reported police encounters, risk-taking behaviors, and unique types and frequency of delinquent acts. We also evaluated effect modification of these relationships by adversity exposure., Results: We observed generally null associations of neurotoxic pesticide use with risk-taking behaviors. Prenatal residential proximity to chlorpyrifos use was associated with higher risk of a police encounter, a delinquent act, and higher incidence of both unique types of acts committed and total frequency of delinquent acts. Prenatal residential proximity to dimethoate use was associated with a higher incidence of police encounters and methomyl with a higher risk of committing a delinquent act. There were no consistent differences when stratified by the number of adverse childhood experiences., Conclusions: We observed mostly null associations between prenatal residential proximity to agricultural pesticide use and risk-taking behaviors at age 18, with little evidence of effect modification by childhood adversity. There were suggestive associations for chlorpyrifos use with having any police encounter and with all measures of delinquent acts that warrant confirmation in other studies., Competing Interests: Declaration of competing interest Dr. Robert Gunier has consulted for law firms in cases involving pesticide exposure and human health. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Gestational diabetes (GDM) is prevalent and benefits from timely and effective treatment, given the short window to impact glycemic control. Clinicians face major barriers to choosing effectively among treatment modalities [medical nutrition therapy (MNT) with or without pharmacologic treatment (antidiabetic oral agents and/or insulin)]. We investigated whether clinical data at varied stages of pregnancy can predict GDM treatment modality., Methods: Among a population-based cohort of 30,474 pregnancies with GDM delivered at Kaiser Permanente Northern California in 2007-2017, we selected those in 2007-2016 as the discovery set and 2017 as the temporal/future validation set. Potential predictors were extracted from electronic health records at different timepoints (levels 1-4): (1) 1-year preconception to the last menstrual period, (2) the last menstrual period to GDM diagnosis, (3) at GDM diagnosis, and (4) 1 week after GDM diagnosis. We compared transparent and ensemble machine learning prediction methods, including least absolute shrinkage and selection operator (LASSO) regression and super learner, containing classification and regression tree, LASSO regression, random forest, and extreme gradient boosting algorithms, to predict risks for pharmacologic treatment beyond MNT., Results: The super learner using levels 1-4 predictors had higher predictability [tenfold cross-validated C-statistic in discovery/validation set: 0.934 (95% CI: 0.931-0.936)/0.815 (0.800-0.829)], compared to levels 1, 1-2, and 1-3 (discovery/validation set C-statistic: 0.683-0.869/0.634-0.754). A simpler, more interpretable model, including timing of GDM diagnosis, diagnostic fasting glucose value, and the status and frequency of glycemic control at fasting during one-week post diagnosis, was developed using tenfold cross-validated logistic regression based on super learner-selected predictors. This model compared to the super learner had only a modest reduction in predictability [discovery/validation set C-statistic: 0.825 (0.820-0.830)/0.798 (95% CI: 0.783-0.813)]., Conclusions: Clinical data demonstrated reasonably high predictability for GDM treatment modality at the time of GDM diagnosis and high predictability at 1-week post GDM diagnosis. These population-based, clinically oriented models may support algorithm-based risk-stratification for treatment modality, inform timely treatment, and catalyze more effective management of GDM., (© 2022. The Author(s).)

Background: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men., Methods: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size)., Results: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum., Conclusions: These findings do not support the role of sex hormones in early colorectal neoplasia among men., Impact: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males., (©2021 American Association for Cancer Research.)

Introduction: Conditional economic incentives are shown to promote medication adherence across a range of health conditions and settings; however, any long-term harms or benefits from these time-limited interventions remain largely unevaluated. We assessed 2-3 years outcomes from a 6-month incentive programme in Tanzania that originally improved short-term retention in HIV care and medication possession., Methods: We traced former participants in a 2013-2016 trial, which randomised 800 food-insecure adults starting HIV treatment at three clinics to receive either usual care (control) or up to 6 months of cash or food transfers (~US$11/month) contingent on timely attendance at monthly clinic appointments. The primary intention-to-treat analysis estimated 24-month and 36-month marginal risk differences (RD) between incentive and control groups for retention in care and all-cause mortality, using multiple imputation for a minority of missing outcomes. We also estimated mortality HRs from time-stratified Cox regression., Results: From 3 March 2018 to 19 September 2019, we determined 36-month retention and mortality statuses for 737 (92%) and 700 (88%) participants, respectively. Overall, approximately 660 (83%) participants were in care at 36 months while 43 (5%) had died. There were no differences between groups in retention at 24 months (86.5% intervention vs 84.4% control, RD 2.1, 95% CI -5.2 to 9.3) or 36 months (83.3% vs 77.8%, RD 5.6, -2.7 to 13.8), nor in mortality at either time point. The intervention group had a lower rate of death during the first 18 months (HR 0.27, 95% CI 0.10 to 0.74); mortality was similar thereafter (HR 1.13, 95% CI 0.33 to 3.79)., Conclusion: These findings confirm that incentives are a safe and effective tool to promote short-term adherence and potentially avert early deaths at the critical time of HIV treatment initiation. Complementary strategies are recommended to sustain lifelong retention in HIV care., Trial Registration Number: NCT01957917., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many adults have risk factors for non-alcoholic fatty liver disease (NAFLD). Screening all adults with risk factors for NAFLD using imaging is not feasible., Objective: To develop a practical scoring tool for predicting NAFLD using participant demographics, medical history, anthropometrics, and lab values., Design: Cross-sectional., Participants: Data came from 6194 white, African American, Hispanic, and Chinese American participants from the Multi-Ethnic Study of Atherosclerosis cohort, ages 45-85 years., Main Measures: NAFLD was identified by liver computed tomography (≤ 40 Hounsfield units indicating > 30% hepatic steatosis) and data on 14 predictors was assessed for predicting NAFLD. Random forest variable importance was used to identify the minimum subset of variables required to achieve the highest predictive power. This subset was used to derive (n = 4132) and validate (n = 2063) a logistic regression-based score (NAFLD-MESA Index). A second NAFLD-Clinical Index excluding laboratory predictors was also developed., Key Results: NAFLD prevalence was 6.2%. The model included eight predictors: age, sex, race/ethnicity, type 2 diabetes, smoking history, body mass index, gamma-glutamyltransferase (GGT), and triglycerides (TG). The NAFLD-Clinical Index model excluded GGT and TG. In the NAFLD-MESA model, the derivation set achieved an AUC NAFLD-MESA = 0.83 (95% CI, 0.81 to 0.86), and the validation set an AUC NAFLD-MESA = 0.80 (0.77 to 0.84). The NAFLD-Clinical Index model was AUC Clinical = 0.78 [0.75 to 0.81] in the derivation set and AUC Clinical = 0.76 [0.72 to 0.80] in the validation set (p Bonferroni-adjusted < 0.01)., Conclusions: The two models are simple but highly predictive tools that can aid clinicians to identify individuals at high NAFLD risk who could benefit from imaging., (© 2021. Society of General Internal Medicine.)

Studies suggest that exposure to pesticides during pregnancy and early childhood is associated with adverse child neurodevelopment. Research to date has focused primarily on exposure to single pesticides or pesticide classes in isolation; there are little data on the effect of exposure to pesticide mixtures on child and adolescent neurodevelopment., Methods: Using California's Pesticide Use Reporting database, we estimated agricultural pesticide use within 1 km of the home during the prenatal and postnatal (ages 0-5 years) periods among participants in the Center for the Health Assessment for Mothers and Children of Salinas (CHAMACOS) birth cohort. We implemented a Bayesian Hierarchical linear mixed-effects model to examine associations with maternal- and youth-reported behavioral and emotional problems from the Behavior Assessment System for Children, 2nd edition (BASC-2) at ages 16 and 18 years (n = 593)., Results: We observed mostly null associations between pesticide applications and neurobehavioral outcomes. There were some trends of modestly increased internalizing behaviors and attention problems in association with organophosphate insecticide use near the home during the prenatal period. In the postnatal period, a two-fold increase in glyphosate applications was associated with more youth-reported depression (β = 1.2, 95% credible intervals [CrI] = 0.2, 2.2), maternal-reported internalizing behaviors (β = 1.23, 95% CrI = 0.2, 2.3), and anxiety (β = 1.2, 95% CrI = 0.2, 2.3). We observed some protective associations with imidacloprid during the prenatal period, particularly in sex-specific analyses., Conclusions: We found only some subtle associations between some pesticides and neurobehavioral outcomes. This study extends previous work by considering potential exposure to mixtures of pesticides., Competing Interests: A.B. is a volunteer member of the Board for The Organic Center, a nonprofit organization addressing scientific issues about organic food and agriculture and is also a member of the USDA National Organic Standards Board. The other authors have no conflicts to report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Prior research suggests a relationship between overall diet quality and breast cancer survival, although few studies have reported on this topic. We evaluated whether 4 dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific, and all-cause mortality., Methods: A total of 3660 women diagnosed with invasive breast cancer were included. Diet was assessed an average of 2.3 (range = 0.7-18.7) months after diagnosis, from which 4 dietary quality indices were derived: the American Cancer Society guidelines (ACS), the alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the 2015 Healthy Eating Index (HEI). Over 40 888 person-years of follow-up, 461 breast cancer recurrences, and 655 deaths were ascertained. Cox models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs)., Results: Adjusted comparisons between extreme quintiles showed all 4 dietary quality indices to be inversely associated with all-cause mortality, suggesting a 21%-27% lower risk (ACS HR = 0.73, 95% CI = 0.56 to 0.95; aMED HR = 0.79, 95% CI = 0.61 to 1.03; DASH HR = 0.76, 95% CI = 0.58 to 1.00; HEI HR = 0.77, 95% CI = 0.60 to 1.01). Similar patterns were noted for non-breast cancer mortality (ACS HR = 0.69, 95% CI = 0.48 to 0.98; aMED HR = 0.73, 95% CI = 0.50 to 1.05; DASH HR = 0.55, 95% CI = 0.38 to 0.79; HEI HR = 0.67, 95% CI = 0.48 to 0.94). None of the dietary quality indices were associated with recurrence or breast cancer-specific mortality., Conclusion: Food intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: To use the case-only gene-environment (G [Formula: see text] E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females., Methods: We studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) [Formula: see text] live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS., Results: Evidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated HLA-DRB1*15:01 allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results., Conclusion: Our findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE 1 ) and 16-hydroxyestrone (16-OHE 1 ) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer., Methods: This population-based study was initiated in 1996-1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE 1 and 16-OHE 1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided., Results: Urinary concentrations of the 2-OHE 1 to 16-OHE 1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; P interaction = .008)., Conclusions: The urinary 2-OHE 1 to 16-OHE 1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) due to shared risk factors with BC and cardiotoxic treatment effects. We aim to investigate racial differences in mortality due to CVD and BC among women diagnosed with invasive BC., Methods: Data from 407 587 non-Hispanic Black (NHB) and White (NHW) women diagnosed with malignant BC (1990-2014) were obtained from the Surveillance, Epidemiology, and End Results database. Cumulative incidence of mortality due to CVD and BC was calculated by race and age (years). Cox models were used to obtain hazard ratios (HR) and 95% confidence intervals (95%CI) for the association of race/ethnicity with cause-specific mortality., Results: The 20-year cumulative incidence of CVD-related mortality was higher among younger NHBs than NHWs (e.g. age 55-69: 13.3% vs 8.9%, respectively). NHBs had higher incidence of BC-specific mortality than NHWs, regardless of age. There was a monotonic reduction in CVD-related mortality disparities with increasing age (age <55: HR = 3.71, 95%CI: 3.29, 4.19; age 55-68: HR = 2.31, 95%CI: 2.15, 2.49; age 69+: HR = 1.24, 95%CI: 1.19, 1.30). The hazard of BC-specific mortality among NHBs was approximately twice that of NHWs (e.g. age <55: HR = 1.98, 95%CI: 1.92, 2.04)., Conclusions: There are substantial differences in mortality due to CVD and BC between NHB and NHW women diagnosed with invasive BC. Racial differences were greatest among younger women for CVD-related mortality and similar across age groups for BC-specific mortality. Future studies should identify pathways through which race/ethnicity affects cause-specific mortality, to inform efforts towards reducing disparities., (© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Previous studies have suggested a "J-shaped" relationship between body mass index (BMI, calculated as weight (kg)/height (m)2) and survival among head and neck cancer (HNC) patients. However, BMI is a vague measure of body composition. To provide greater resolution, we used Bayesian sensitivity analysis, informed by external data, to model the relationship between predicted fat mass index (FMI, adipose tissue (kg)/height (m)2), lean mass index (LMI, lean tissue (kg)/height (m)2), and survival. We estimated posterior median hazard ratios and 95% credible intervals for the BMI-mortality relationship in a Bayesian framework using data from 1,180 adults in North Carolina with HNC diagnosed between 2002 and 2006. Risk factors were assessed by interview shortly after diagnosis and vital status through 2013 via the National Death Index. The relationship between BMI and all-cause mortality was convex, with a nadir at 28.6, with greater risk observed throughout the normal weight range. The sensitivity analysis indicated that this was consistent with opposing increases in risk with FMI (per unit increase, hazard ratio = 1.04 (1.00, 1.08)) and decreases with LMI (per unit increase, hazard ratio = 0.90 (0.85, 0.95)). Patterns were similar for HNC-specific mortality but associations were stronger. Measures of body composition, rather than BMI, should be considered in relation to mortality risk., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Previous studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)., Methods: This study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1.2) months of diagnosis, covariates were collected from electronic health records, and vital status was assessed by death records. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression., Results: SAT and VAT ranged from 19.0 to 891 cm 2 and from 0.484 to 454 cm 2 , respectively. SAT was related to increased risk of death (127-cm 2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm 2 increase; HR [95% CI]: 1.02 [0.91-1.14]). An association with VAT was noted among women with stage II cancer (stage II: HR: 1.17 [95% CI: 0.99-1.39]; stage III: HR: 0.90 [95% CI: 0.76-1.07]; P interaction < 0.01). Joint increases in SAT and VAT were associated with mortality above either alone (simultaneous 1-SD increase: HR 1.19 [95% CI: 1.05-1.34])., Conclusions: SAT may be an underappreciated risk factor for breast cancer-related death., (© 2019 The Obesity Society.)

Importance: Use of alternative tobacco products (ATPs) such as electronic cigarettes, chewing tobacco, pipes, cigars, cigarillos, little cigars, and hookah is rapidly increasing. Although marketing restrictions exist for cigarettes, marketing of ATPs is not yet fully regulated, and studies have not assessed the association between ownership of ATP promotional materials and subsequent ATP or cigarette initiation among adolescents and young adults., Objective: To estimate the association between marketing receptivity measured at baseline and ATP and any tobacco initiation 1 year later, including cigarettes, among adolescents and young adults., Design, Setting, and Participants: Longitudinal cohort study of adolescents and young adults aged 13 to 19 years recruited at high schools in California from July 2014 to October 2015, with follow-up 1 year later. Data were analyzed from January to March 2018., Exposures: Ownership of ATP-specific promotional material and ownership of any tobacco promotional materials (eg, samples, coupons, branded caps, t-shirts, or posters) assessed in wave 1., Main Outcomes and Measures: Outcomes were (1) ATP initiation and (2) either ATP or cigarette initiation in wave 2., Results: Of 757 participants (mean [SD] age at wave 1, 16.1 [1.1] years; 481 [63.5%] female; 166 [21.9%] Asian or Pacific Islander, 202 [26.7%] white, and 276 [36.4%] Latino), 129 (17.0%) initiated ATP use and 141 (18.6%) initiated ATP or cigarette use 1 year later. In unadjusted models, wave 2 ATP initiation was found to be significantly associated with wave 1 ownership of ATP promotional materials (odds ratio, 2.23; 95% CI, 1.26-3.97). After adjustment for wave 1 demographic covariates, the association between ownership of ATP promotional material and ATP initiation 1 year later yielded similar results (odds ratio, 2.13; 95% CI, 1.16-3.91). Results of models assessing a combined outcome variable of either ATP or cigarette ever use were not statistically significant., Conclusions and Relevance: Ownership of ATP promotional materials was associated with subsequent initiation of ATPs. The results of this study are consistent with the suggestion that current marketing restrictions for cigarettes, including restrictions of the distribution of samples, coupons, and other promotional material, should extend to ATPs.

Objectives Shift work, such as alternating day and nights, causes chronobiologic disruptions which may cause an increase in hypertension risk. However, the relative contributions of the components of shift work ‒ such as shift type (eg, night work) and rotations (ie, switching of shift times; day to night) ‒ on this association are not clear. To address this question, we constructed novel definitions of night work and rotational work and assessed their associations with risk of incident hypertension. Methods A cohort of 2151 workers at eight aluminum manufacturing facilities previously studied for cardiovascular disease was followed from 2003 through 2013 for incident hypertension, as defined by ICD-9 insurance claims codes. Detailed time-registry data was used to classify each worker's history of rotational and night work. The associations between recent rotational work and night work in the last 12 months and incident hypertension were estimated using adjusted Cox proportional hazards models. Results Elevated hazard ratios (HR) were observed for all levels of recent night work (>0-5, >5-50, >50-95, >95-100%) compared with non-night workers, and among all levels of rotational work (<1, 1-10, >10-20, >20-30, and >30%) compared with those working <1% rotational work. In models for considering the combination of night and rotational work, workers with mostly night work and frequent rotations (≥50% night and ≥10% rotation) had the highest risk of hypertension compared to non-night workers [HR 4.00, 95% confidence interval (CI )1.69-9.52]. Conclusions Our results suggest recent night and rotational work may both be associated with higher rates of incident hypertension.

Metalworking fluids (MWFs) are a class of complex mixtures of chemicals and oils, including several known carcinogens that may pose a cancer hazard to millions of workers. Reports on the relation between MWFs and incident colon cancer have been mixed., Methods: We investigated the relation between exposure to straight, soluble, and synthetic MWFs and the incidence of colon cancer in a cohort of automobile manufacturing industry workers, adjusting for time-varying confounding affected by prior exposure to reduce healthy worker survivor bias. We used longitudinal targeted minimum loss-based estimation (TMLE) to estimate the difference in the cumulative incidence of colon cancer comparing counterfactual outcomes if always exposed above to always exposed below an exposure cutoff while at work. Exposure concentration cutoffs were selected a priori at the 90th percentile of total particulate matter for each fluid type: 0.034, 0.400, and 0.003 for straight, soluble, and synthetic MWFs, respectively., Results: The estimated 25-year risk differences were 3.8% (95% confidence interval [CI] = 0.7, 7.0) for straight, 1.3% (95% CI = -2.3, 4.8) for soluble, and 0.2% (95% CI = -3.3, 3.7) for synthetic MWFs, respectively. The corresponding risk ratios were 2.39 (1.12, 5.08), 1.43 (0.67, 3.04), and 1.08 (0.51, 2.30) for straight, soluble, and synthetic MWFs, respectively., Conclusions: By controlling for time-varying confounding affected by prior exposure, a key feature of occupational cohorts, we were able to provide evidence for a causal effect of straight MWF exposure on colon cancer risk that was not found using standard analytical techniques in previous reports., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report.Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.)

Breast cancer is the leading cancer diagnosed among women, and environmental studies have produced few leads on modifiable risk factors for breast cancer. Following an Institute of Medicine recommendation for occupational studies of women highly exposed to potential breast cancer risk factors, we took advantage of an existing cohort of 4,503 female autoworkers in Michigan exposed to metalworking fluid (MWF), complex mixtures of oils and chemicals widely used in metal manufacturing worldwide. Cox proportional hazards models were fit to estimate hazard ratios for incident breast cancer (follow-up, 1985-2013) and cumulative exposure (20-year lag) to straight mineral oils (a known human carcinogen) and water-based soluble and synthetic MWF. Because the state cancer registry began decades after the cohort was defined, we restricted our analyses to subcohorts of women hired closer to the start of follow-up. Among those hired after 1969, the hazard ratio associated with a 1 interquartile-range increase in straight MWF exposure was 1.13 (95% confidence interval: 1.03, 1.23). In separate analyses of premenopausal breast cancer, defined by age at diagnosis, the hazard ratio was elevated for exposure to synthetic MWF (chemical lubricants with no oil content), possibly suggesting a different mechanism in the younger women with breast cancer. This study adds to the limited literature regarding quantitative chemical exposures and breast cancer risk.

Background: During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival., Methods: We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively., Results: EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ≥ weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival., Conclusions: If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

Background: The purpose of this study was to examine whether at-diagnosis smoking and postdiagnosis changes in smoking within five years after breast cancer were associated with long-term all-cause and breast cancer-specific mortality., Methods: A population-based cohort of 1508 women diagnosed with first primary in situ or invasive breast cancer in 1996 to 1997 were interviewed shortly after diagnosis and again approximately five years later to assess smoking history. Participants were followed for vital status through December 31, 2014. After 18+ years of follow-up, 597 deaths were identified, 237 of which were breast cancer related. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Compared with never smokers, risk of all-cause mortality was elevated among the 19% of at-diagnosis smokers (HR=1.69, 95% CI=1.36 to 2.11), those who smoked 20 or more cigarettes per day (HR=1.85, 95% CI=1.42 to 2.40), women who had smoked for 30 or more years (HR=1.62, 95% CI=1.28 to 2.05), and women who had smoked 30 or more pack-years (HR=1.82, 95% CI=1.39 to 2.37). Risk of all-cause mortality was further increased among the 8% of women who were at-/post-diagnosis smokers (HR=2.30, 95% CI=1.56 to 3.39) but was attenuated among the 11% women who quit smoking after diagnosis (HR=1.83, 95% CI=1.32 to 2.52). Compared with never smokers, breast cancer-specific mortality risk was elevated 60% (HR=1.60, 95% CI=0.79 to 3.23) among at-/postdiagnosis current smokers, but the confidence interval included the null value and elevated 175% (HR=2.75, 95% CI=1.26 to 5.99) when we considered postdiagnosis cumulative pack-years. Conclusions: Smoking negatively impacts long-term survival after breast cancer. Postdiagnosis cessation of smoking may reduce the risk of all-cause mortality. Breast cancer survivors may benefit from aggressive smoking cessation programs starting as early as the time of diagnosis., Competing Interests: Notes: H. Parada declares that he has no conflict of interest. P. T. Bradshaw declares that he has no conflict of interest. S. E. Steck declares that she has no conflict of interest. L. S. Engel declares that he has no conflict of interest. K. Conway declares that she has no conflict of interest. S. L. Teitelbaum declares that she has no conflict of interest. A. I. Neugut declares that he has no conflict of interest. R. M. Santella declares that she has no conflict of interest. M. D. Gammon declares that she has no conflict of interest.

Background: Mechanisms underlying the inverse association between physical activity and survival after breast cancer are unresolved, but DNA methylation may play a role. We hypothesized that promoter methylation of breast cancer-related genes, as well as global methylation, may modify the association between prediagnostic recreational physical activity (RPA) and breast cancer mortality., Methods: Using a population-based sample of 1254 women diagnosed with first primary breast cancer, we examined modification of the RPA-mortality association by gene-specific promoter methylation and global methylation. Average lifetime RPA was assessed from menarche to diagnosis through structured in-home interviews. Promoter methylation of 13 breast cancer-related genes was evaluated in archived tumor by methylation-specific polymerase chain reaction and MethyLight assay. Global methylation in white blood cell DNA was determined at long interspersed nucleotide element 1 and by the luminometric methylation assay. After approximately 15 years of follow-up, 486 patients had died, and 186 of the deaths were breast cancer-related. We used Cox proportional hazards regression to estimate HRs and 95% CIs as well as likelihood ratio tests to assess multiplicative interactions., Results: All-cause mortality was lower only among physically active women with methylated promoter of APC (HR 0.60, 95% CI 0.40-0.80), CCND2 (HR 0.56, 95% CI 0.32-0.99), HIN (HR 0.55, 95% CI 0.38-0.80), and TWIST1 (HR 0.28, 95% CI 0.14-0.56) in tumors, but not among those with unmethylated tumors (significant interaction p < 0.05). We found no interaction between RPA and global methylation., Conclusions: The improved survival after breast cancer that is associated with RPA may be more pronounced in women with promoter tumor methylation in biologically plausible genes.

Background: Environmental tobacco smoke (ETS) exposure is hypothesized to influence survival after breast cancer, but few studies have examined this association., Methods: A population-based cohort of women (N = 1,508) diagnosed with first primary invasive or in situ breast cancer in 1996 to 1997 was interviewed shortly after diagnosis and again approximately 5 years later to assess ETS exposure, and women were followed for more than 18 years using the National Death Index; 597 deaths (237 associated with breast cancer) were identified. Multivariable Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for mortality among women with breast cancer as related to at-diagnosis and at-/postdiagnosis changes in ETS exposure., Results: There was little or no association between at-diagnosis ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78-1.40) or breast cancer-specific (HR = 0.98; 95% CI, 0.63-1.52) mortality. Mortality was elevated among women who reported cessation in postdiagnosis ETS exposure up to 1 year before the follow-up assessment, for all-cause (HR = 1.81; 95% CI, 0.87-3.74) and breast cancer mortality (HR = 1.89; 95% CI, 0.68-5.24); however, estimates were imprecise., Conclusions: We found little evidence of an association between at-diagnosis ETS exposure and mortality after breast cancer. Postdiagnosis cessation of ETS exposure was positively associated with mortality, although we could not rule out chance and reverse causation as possible explanations., Impact: Exposure to ETS does not appear to influence mortality after breast cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 278-80. ©2016 AACR., Competing Interests: Conflicts of Interest: None declared, (©2016 American Association for Cancer Research.)

Background: Grilled, barbecued, and smoked meat intake, a prevalent dietary source of polycyclic aromatic hydrocarbon (PAH) carcinogens, may increase the risk of incident breast cancer. However, no studies have examined whether intake of this PAH source influences survival after breast cancer., Methods: We interviewed a population-based cohort of 1508 women diagnosed with first primary invasive or in situ breast cancer in 1996 and 1997 at baseline and again approximately five years later to assess grilled/barbecued and smoked meat intake. After a median of 17.6 years of follow-up, 597 deaths, of which 237 were breast cancer related, were identified. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality as related to prediagnosis intake, comparing high (above the median) to low intake, as well as postdiagnosis changes in intake, comparing every combination of pre-/postdiagnosis intake to low pre-/postdiagnosis intake. All statistical tests were two-sided., Results: High prediagnosis grilled/barbecued and smoked meat intake was associated with increased risk of all-cause mortality (HR = 1.23, 95% CI = 1.03 to 1.46). Other associations were noted, but estimates were not statistically significant. These include high prediagnosis smoked beef/lamb/pork intake and increased all-cause (HR = 1.17, 95% CI = 0.99 to 1.38, P trend = .10) and breast cancer-specific (HR = 1.23, 95% CI = 0.95 to 1.60, P trend = .09) mortality. Also, among women with continued high grilled/barbecued and smoked meat intake after diagnosis, all-cause mortality risk was elevated 31% (HR = 1.31, 95% CI = 0.96 to 1.78). Further, breast cancer-specific mortality was decreased among women with any pre- and postdiagnosis intake of smoked poultry/fish (HR = 0.55, 95% CI = 0.31 to 0.97)., Conclusion: High intake of grilled/barbecued and smoked meat may increase mortality after breast cancer., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction., Objectives: This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures., Methods: In a population-based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake., Results: Most women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.40) and synthetic firelog burning (OR=1.29, 95%CrI=1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.45, 95%CrI=1.02, 2.04)., Conclusions: Groups of PAH sources, particularly indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Breast cancer patients commonly report using >1 form of complementary and alternative medicine (CAM). However, few studies have attempted to analyze predictors and outcomes of multiple CAM modalities. We sought to group breast cancer patients by clusters of type and intensity of complementary and alternative medicine (CAM) use following diagnosis., Methods: Detailed CAM use following breast cancer diagnosis was assessed in 2002-2003 among 764 female residents of Long Island, New York diagnosed with breast cancer in 1996-1997. Latent class analysis (LCA) was applied to CAM modalities while taking into account frequency and intensities., Results: Four distinct latent classes of CAM use emerged: 1) "Low-dose supplement users" (40%), who used only common nutritional supplements; 2) "Vitamin/mineral supplement users" (39%), using an abundance of supplements in addition to other practices; 3) "Mind-body medicine users" (12%), with near-universal use of supplements, mind-body medicine techniques, and massage; and 4) "Multi-modality high-dose users" (9%), who were highly likely to use nearly all types of CAM. Predictors of membership in classes with substantial CAM use included younger age, more education, higher income, Jewish religion, ideal body mass index, higher fruit and vegetable intake, higher levels of physical activity, receipt of adjuvant chemotherapy, and prior use of oral contraceptives., Conclusions: LCA identified important subgroups of breast cancer patients characterized by varying degrees of complementary therapy use. Further research should explore the reproducibility of these classes and investigate the association between latent class membership and breast cancer outcomes.

Aspirin has been shown to protect against colorectal neoplasms; however, the optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to study the relationship between prostanoid metabolites and aspirin's effect on adenoma occurrence. We used data from the Aspirin/Folate Polyp Prevention Study, in which 1,121 participants with a recent adenoma were randomized to placebo or two doses of aspirin (81 or 325 mg/d) to be taken until the next surveillance colonoscopy, anticipated about 3 years later. Urinary metabolites of prostanoids (PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass spectrometry or GC/NICI-MS in 876 participants near the end of treatment follow-up. Poisson regression with a robust error variance was used to calculate relative risks and 95% confidence intervals. PGE-M, PGI-M, and dTxB2 levels were 28%, 37%, and 60% proportionately lower, respectively, in individuals who took 325 mg of aspirin compared with individuals who took placebo (all P < 0.001). Similarly, among individuals who took 81 mg of aspirin, PGE-M, PGI-M, and dTxB2 were, respectively, 18%, 30%, and 57% proportionally lower compared with placebo (all P < 0.005). None of the metabolites or their ratios were statistically significantly associated with the risk of adenoma occurrence. The effect of aspirin in reducing adenoma risk was independent of prostanoid levels. Aspirin use is associated with lower levels of urinary prostanoid metabolites. However, our findings do not support the hypothesis that these metabolites are associated with adenoma occurrence, suggesting that COX-dependent mechanisms may not completely explain the chemopreventive effect of aspirin on colorectal neoplasms., (©2015 American Association for Cancer Research.)

The fraction of the obese population who appear to be free of the metabolic abnormalities that usually accompany excess adiposity has garnered a great deal of attention recently. The so-called "metabolically healthy obesity" concept is thought to offer a refinement of the traditional obesity definitions that are based solely on anthropometry. The commentary by Rey-López et al. (Am J Epidemiol. 2015;182(9):737-741) in this issue of the Journal highlights several limitations of the "metabolically healthy obesity" concept and calls into question its usefulness as a public health metric. We discuss several of the issues raised by these authors and offer some perspective on why the utility of this concept remains unresolved., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: Approximately 17% of obese Americans are free of the cardiometabolic risk factors, but few studies have compared responses to weight change in metabolically healthy obese (MHO) and metabolically healthy normal weight (MHNW) adults. We compared the impact of weight loss, weight maintenance and weight gain on cardiometabolic risk factors in the MHO and the MHNW., Subjects/methods: Data were from the Atherosclerosis Risk in Communities (ARIC) study. Multiple observations on 2710 participants were included, yielding 4541 observations of sequential 3-year intervals. Metabolically healthy was defined as absence of all components of metabolic syndrome excluding waist circumference. Mixed effects models were used to compare changes in each of five cardiometabolic risk factors within weight change categories (<-3% for weight loss, ±3% for weight maintenance and >3% for weight gain)., Results: Weight loss was associated with comparable small changes or no changes in cardiometabolic risk factors in MHO and MHNW individuals. Weight gain was associated with larger increases in systolic (8.6 vs 6.2 mm Hg) and diastolic (3.9 vs 2.5 mm Hg) blood pressure, triglycerides (21.9 vs 15.8 mg/dl) and glucose (4.9 vs 1.9 mg/dl) in MHO individuals compared with MHNW individuals. Weight maintenance was associated with larger increases in triglycerides (10.0 vs 6.4 mg/dl) and glucose (1.7 vs 0.9 mg/dl) in MHO compared with MHNW individuals. MHO weight losers had more favorable changes in the five cardiometabolic risk factors compared to MHO weight maintainers (P<0.02) or gainers (P<0.0001)., Conclusions: This work showed differences between MHNW and MHO adults and supports recommendations for weight loss in the MHO in order to avoid increases in risk factors associated with weight maintenance and weight gain.

Introduction: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk., Methods: Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA)., Results: The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater than two-fold increased risk of postmenopausal breast cancer (BMI<25kg/m2: OR=2.16; 95% CI=1.35, 3.57 and BMI 25-29.9kg/m2: OR=2.96; 95% CI=1.69, 5.19) compared to women in the lowest LUMA quartile. Similar increases in the LUMA-breast cancer association were observed among women who were physically active (moderate RPA: OR=2.62; 95% CI=1.44, 4.75 and high RPA: OR=2.62; 95% CI=1.53, 4.49). Estimates among obese and inactive women were less pronounced and imprecise. Although we observed statistical interactions (p<0.05) between BMI and RPA with LINE-1, we were unable to discern any clear associations with breast cancer., Conclusions: The association between LUMA and postmenopausal breast cancer risk may be modified by postmenopausal body size and physical activity.

Background: Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival., Methods: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively., Results: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide., Conclusions: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.

The Obesity Paradox could result in confusing messages that derail beneficial environmental changes and lead to reduced efforts by physicians to provide healthy lifestyle treatment plans to their obese patients. The Obesity Paradox applies in the main to individuals who have a disease, and therefore observed associations with mortality illustrating the Paradox may be more susceptible to certain types of bias than would be found in healthy individuals. Although individualization of weight loss advice for patients with serious disease is appropriate in medical settings, this does not supplant the need for general efforts to prevent and treat obesity.

Background and Objectives: Cross-sectional studies indicate that adaptation to Western norms, especially at a younger age, might explain the higher average body mass index (BMI) among Asians living in the United States (US) compared to Asians living in Asia. However, migrants differ from non-migrants in sociocultural factors that are difficult to measure and, thus, longitudinal studies on the same individuals prior to and after immigration are needed. The objective of this study was to determine differences in changes in BMI across age by residence (US or Asia) and age at immigration using longitudinal data on BMI prior to and after immigration., Methods and Study Design: The California Men's Health Study includes 1,549 foreign-born Asian men who were aged 44-71 at baseline in 2002-03. BMI at ages 30, 40, 50 and 60 was calculated using self-reported weight history and current height. Residence at each age decade and age at immigration were determined. Data were analyzed using generalized estimating equations., Results: Ten-year BMI increases were smaller among Asians who lived in Asia prior to migrating to the US compared to those who already lived in the US. This effect was most evident be-tween ages 30-40 when Asians in Asia had a 0.69 kg/m2 (95% CI: -1.08, -0.30) smaller increase in BMI. Immigrants who moved to the US before age 40 experienced greater increases in BMI than immigrants who moved to the US at an older age., Conclusion: This study is the first to support the hypothesis that living in the US and younger age at immigration results in larger BMI increases in Asian men.

Increased physical activity has been shown to be protective for breast cancer although few studies have examined this association in Black women. In addition, limited evidence to date indicates that sedentary behavior may be an independent risk factor for breast cancer. We examined sedentary behavior and physical activity in relation to subsequent incident breast cancer in a nested case-control study within 546 cases (374 among Black women) and 2,184 matched controls enrolled in the Southern Community Cohort Study. Sedentary and physically active behaviors were assessed via self-report at study baseline (2002-2009) using a validated physical activity questionnaire. Conditional logistic regression was used to estimate mutually adjusted ORs and corresponding 95% confidence intervals (CI) for quartiles of sedentary and physical activity measures in relation to breast cancer risk. Being in the highest versus lowest quartile of total sedentary behavior (≥ 12 vs. <5.5 h/d) was associated with increased odds of breast cancer among White women [OR, 1.94 (95% CI, 1.01-3.70); P trend = 0.1] but not Black women [OR, 1.23 (95% CI, 0.82-1.83); P trend = 0.6] after adjustment for physical activity. After adjustment for sedentary activity, greater physical activity was associated with reduced odds for breast cancer among White women (P trend = 0.03) only. In conclusion, independent of one another, sedentary behavior and physical activity are risk factors for breast cancer among White women. Differences in these associations between Black and White women require further investigation. Reducing sedentary behavior and increasing physical activity are potentially independent targets for breast cancer prevention interventions.

Objective: There is recent interest in characterizing the subset of obese (OB) individuals who have healthy metabolic profiles yet only two studies have examined this group prospectively but not in racially diverse populations., Design and Methods: We analyzed factors associated with the prevalence and incidence of metabolic syndrome (MetSyn) among individuals grouped by BMI categories in a multi-center, community-based cohort of 14,663 African-American and white men and women aged 45-64 years at recruitment in 1987-1989, the Atherosclerosis Risk in Communities (ARIC) Study. Logistic and proportional hazards regression were utilized to estimate odds ratios (ORs) for the prevalence and hazard ratios (HRs) for incidence of MetSyn with 95% confidence intervals (CIs)., Results: At visit 1, MetSyn was positively associated with age, female gender, African-American race, and inversely related to education, associations being more pronounced among normal weight (NW) subjects. Among those without MetSyn at visit 1, OB subjects were more likely to develop MetSyn compared with NW (HR (95% CI): 4.53 (4.09-5.01)). Several factors were associated with incident MetSyn among NW, including older age (per year: 1.05 (1.03-1.06)), female gender (vs. male: 1.29 (1.10-1.52)), heavy alcohol intake (vs. never: 0.75 (0.59-0.94)), and physical activity (tertile 3 vs. tertile 1: 0.71 (0.58-0.86)) but not OB. Weight gain (>5%) was also more highly associated with MetSyn in NW (1.61 (1.28-2.02)) compared with OB (1.01 (0.85-1.20))., Conclusions: We conclude that lifestyle factors may play a stronger role in the development of MetSyn in NW individuals compared with OB and that metabolically healthy obesity may not be a stable condition., (Copyright © 2012 The Obesity Society.)