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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.

BackgroundPrenatal 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.ObjectivesEvaluate 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.MethodsParticipants 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.ResultsWe 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.ConclusionsWe 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.

BackgroundGestational 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.MethodsAmong 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.ResultsThe 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)].ConclusionsClinical 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.

PurposePopulation-based surveys are possible sources from which to draw representative control data for case-control studies. However, these surveys involve complex sampling that could lead to biased estimates of measures of association if not properly accounted for in analyses. Approaches to incorporating complex-sampled controls in density-sampled case-control designs have not been examined.MethodsWe used a simulation study to evaluate the performance of different approaches to estimating incidence density ratios (IDR) from case-control studies with controls drawn from complex survey data using risk-set sampling. In simulated population data, we applied four survey sampling approaches, with varying survey sizes, and assessed the performance of four analysis methods for incorporating survey-based controls.ResultsEstimates of the IDR were unbiased for methods that conducted risk-set sampling with probability of selection proportional to survey weights. Estimates of the IDR were biased when sampling weights were not incorporated, or only included in regression modeling. The unbiased analysis methods performed comparably and produced estimates with variance comparable to biased methods. Variance increased and confidence interval coverage decreased as survey size decreased.ConclusionsUnbiased estimates are obtainable in risk-set sampled case-control studies using controls drawn from complex survey data when weights are properly incorporated.

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 remainlargely 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 eitherusual care (control) or up to 6 months of cash or food transfers (~US$11/month) contingent on timely attendance at monthly clinic appointments. The primaryintention-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 statusesfor 737 (92%) and 700 (88%) participants, respectively. Overall, approximately 660 (83%) participants were in care at 36 months while 43 (5%) had died. Therewere 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 0.33to 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 thecritical time of HIV treatment initiation. Complementary strategies are recommended to sustain lifelongretention in HIV care.Trial registration number NCT01957917

PurposeTo estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association.MethodsData came from 4,522 adults ages 45-84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications.ResultsOver a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5).ConclusionsThese data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.

BackgroundMany adults have risk factors for non-alcoholic fatty liver disease (NAFLD). Screening all adults with risk factors for NAFLD using imaging is not feasible.ObjectiveTo develop a practical scoring tool for predicting NAFLD using participant demographics, medical history, anthropometrics, and lab values.DesignCross-sectional.ParticipantsData came from 6194 white, African American, Hispanic, and Chinese American participants from the Multi-Ethnic Study of Atherosclerosis cohort, ages 45-85 years.Main measuresNAFLD 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 resultsNAFLD 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 AUCNAFLD-MESA = 0.83 (95% CI, 0.81 to 0.86), and the validation set an AUCNAFLD-MESA = 0.80 (0.77 to 0.84). The NAFLD-Clinical Index model was AUCClinical = 0.78 [0.75 to 0.81] in the derivation set and AUCClinical = 0.76 [0.72 to 0.80] in the validation set (pBonferroni-adjusted < 0.01).ConclusionsThe two models are simple but highly predictive tools that can aid clinicians to identify individuals at high NAFLD risk who could benefit from imaging.

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.MethodsUsing 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).ResultsWe 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.ConclusionsWe found only some subtle associations between some pesticides and neurobehavioral outcomes. This study extends previous work by considering potential exposure to mixtures of pesticides.

BackgroundPrior 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.MethodsA 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).ResultsAdjusted 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.ConclusionFood intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer.

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to

In the United States, obesity has increased in prevalence over time and is strongly associated with subsequent outcomes such as diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). It is unclear, however, as to how the magnitude of NAFLD risk from obesity and DM is increased in safety-net health system settings. Among the San Francisco Health Network (SFHN) patients (N = 47,211), we examined the association between Body Mass Index (BMI) and elevated liver enzyme levels, including interaction by DM status. Our findings revealed that 32.2 percent of SFHN patients were obese, and Pacific Islanders in the safety-net had the highest rates of obesity compared to other racial groups, even after using higher race-specific BMI cutoffs. In SFHN, obesity was associated with elevated liver enzymes, with the relationship stronger among those without DM. Our findings highlight how obesity is a stronger factor of NAFLD in the absence of DM, suggesting that practitioners consider screening for NAFLD among safety-net patients with obesity even if DM has not developed. These results highlight the importance of directing efforts to reduce obesity in safety-net health systems and encourage researchers to further examine effect modification between health outcomes in such populations.

PurposeThe rise of noncigarette, alternative tobacco product (ATP) use among adolescents may be due in part to an increase in retail availability of ATPs. We examined whether proximity and density of tobacco retailers near students' homes are associated with a higher likelihood of initiating ATP use over time.MethodsUsing data from 728 adolescents (aged 13-19 years at baseline) residing in 191 different neighborhoods and attending 10 different California high schools, longitudinal multilevel and cross-classified random effect models evaluated individual-level, neighborhood-level, and school-level risk factors for ATP initiation after 1 year. Covariates were obtained from the American Community Survey and the California Department of Education.ResultsThe sample was predominantly female (63.5%) and was racially and ethnically diverse. Approximately one third of participants (32.5%) reported ever ATP use at baseline, with 106 (14.5%) initiating ATP use within 1 year. The mean number of tobacco retailers per square mile within a tract was 5.66 (standard deviation = 6.3), and the average distance from each participant's residence to the nearest tobacco retailer was .61 miles (standard deviation = .4). Living in neighborhoods with greater tobacco retailer density at baseline was associated with higher odds of ATP initiation (odds ratio = 1.22, 95% confidence interval = 1.07-2.12), controlling for individual and school factors.ConclusionsTobacco retailers clustered in students' home neighborhood may be an environmental influence on adolescents' ATP use. Policy efforts to reduce adolescent ATP use should aim to reduce the density of tobacco retailers and limit the proximity of tobacco retailers near adolescents' homes and schools.

BackgroundThe authors hypothesized that epigenetic changes may help to clarify the underlying biologic mechanism linking aspirin use to breast cancer prognosis. To the authors' knowledge, this is the first epidemiologic study to examine whether global methylation and/or tumor promoter methylation of breast cancer-related genes interact with aspirin use to impact mortality after breast cancer.MethodsPrediagnosis aspirin use was assessed through in-person interviews within a population-based cohort of 1508 women diagnosed with a first primary breast cancer in 1996 and 1997. Global methylation in peripheral blood was assessed by long interspersed elements-1 (LINE-1) and the luminometric methylation assay. Promoter methylation of 13 breast cancer-related genes was measured in tumor by methylation-specific polymerase chain reaction and the MethyLight assay. Vital status was determined by the National Death Index through December 31, 2014 (N = 202/476 breast cancer-specific/all-cause deaths identified among 1266 women with any methylation assessment and complete aspirin data). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs, and the likelihood ratio test was used to evaluate multiplicative interactions.ResultsAll-cause mortality was elevated among aspirin users who had methylated promotor of BRCA1 (HR, 1.67; 95% CI, 1.26-2.22), but not among those with unmethylated promoter of BRCA1 (HR, 0.99; 95% CI, 0.67-1.45; P for interaction ≤.05). Decreased breast cancer-specific mortality was observed among aspirin users who had unmethylated promotor of BRCA1 and PR and global hypermethylation of LINE-1 (HR, 0.60, 0.78, and 0.63, respectively; P for interaction ≤.05), although the 95% CIs included the null.ConclusionsThe current study suggests that the LINE-1 global methylation and promoter methylation of BRCA1 and PR in tumor may interact with aspirin use to influence mortality after breast cancer.

ObjectivePrevious studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).MethodsThis 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.ResultsSAT and VAT ranged from 19.0 to 891 cm2 and from 0.484 to 454 cm2 , respectively. SAT was related to increased risk of death (127-cm2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm2 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

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 (10-20, >20-30, and >30%) compared with those working

Background: Older head and neck cancer (HNC) survivors have concerning rates of potentially unsafe opioid prescribing. Identifying the specialties of opioid prescribers for HNC survivors is critical for targeting the settings for opioid safety interventions. This study hypothesized that oncology and surgery providers are primarily responsible for opioid prescriptions in the year after treatment but that primary care providers (PCPs) are increasingly involved in prescribing over time. Methods: Using linked Surveillance, Epidemiology, and End Results–Medicare data, a retrospective analysis was conducted of adults aged >65 years diagnosed between 2014 and 2017 with stage I–III HNC and who had ≥6 months of treatment‐free follow‐up through 2019. Starting at treatment completion, opioid fills were assigned to a prescriber specialty: oncology, surgery, primary care, pain management, or other. Prescriber patterns were summarized for each year of follow‐up. Multinomial logistic regression models captured the likelihood of opioids being prescribed by each specialty. Results: Among 5135 HNC survivors, 2547 (50%) had ≥1 opioid fill (median, 2.1‐year follow‐up). PCPs prescribed 47% of all fills (42%–55% each year). PCPs prescribed opioids to 45% of survivors with ≥1 opioid fill, which was a greater share than other specialties. PCPs prescribed longer supplies of opioids (median, 20 days/fill; median, 30 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncology provider was four times lower than that of it being prescribed by a PCP. Conclusions: PCP involvement in opioid prescribing remains high throughout HNC survivorship. Interventions to improve the safety of opioid prescribing should target primary care, as is typical for opioid reduction efforts in the noncancer population. Half of older head and neck cancer (HNC) survivors, who experience a high burden of pain after treatment completion, fill opioid prescriptions in the early years after treatment completion, and those who fill opioid prescriptions are most likely to have their opioids prescribed by a primary care provider. Further exploration of opioid safety among HNC survivors, and interventions to improve opioid safety, should focus largely on primary care settings in the early years after treatment completion. [ABSTRACT FROM AUTHOR]

Background: Body composition may be related to survival in patients with clear-cell renal cell carcinoma (ccRCC), but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity. Methods: We analyzed data from 1,022 patients with ccRCC who underwent nephrectomy between 2000 and 2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose tissue, and subcutaneous adipose tissue indexes (cm2/m2) and radiodensities [Hounsfield units (HU)] were assessed from noncontrast presurgical CT scans; clinical and demographic characteristics were available from the time of surgery. HRs and confidence intervals were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures. Results: The median age of the patients was 58 years, 69% were male, and 90% were White. There were 169 OS events over 8,392 person-years and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower skeletal muscle radiodensity [-10 HU, HR (95% confidence interval), 1.37 (1.05-1.77)] and greater visceral adipose tissue radiodensity [+10 HU, 1.66 (1.06-2.59)], with similar findings for DFS. Poor survival was also associated with greater visceral adipose tissue index [+40 cm2/m2, OS: 1.32 (0.97, 1.79); DFS: 1.33 (1.04, 1.71)]. Associations with skeletal muscle radiodensity were limited to patients with stage 1/2 disease. Conclusions: Radiodensities of skeletal muscle and visceral adipose tissues may be novel presurgical prognostic factors for patients with ccRCC. [ABSTRACT FROM AUTHOR]

Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making  $50,000/year [OR 2.47 (1.69-3.25); p interaction  $50,000/year [1.28 (0.97-1.58); p interaction

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. 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. 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, Ptrend = .10) and breast cancer-specific (HR = 1.23, 95% CI = 0.95 to 1.60, Ptrend = .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). High intake of grilled/barbecued and smoked meat may increase mortality after breast cancer.

BackgroundAchieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results.MethodsWe examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer-specific mortality in a cohort of n = 12,590 stage I-III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0-9) years]. We divided follow-up into earlier (18-54 months) and later (>54 months) postdiagnosis periods.ResultsMean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (≥10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12-3.26) earlier and 1.60 (1.14-2.25) later in follow-up. Modest losses (>5%-

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. [ABSTRACT FROM AUTHOR]

Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43-4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43-12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19-2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45-4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.

BackgroundCardiovascular disease (CVD) is of increasing concern among breast cancer survivors. However, the burden of this comorbidity in this group relative to the general population, and its temporal pattern, remains unknown.MethodsWe compared deaths due to CVD in a population-based sample of 1,413 women with incident breast cancer diagnosed in 1996-1997, and 1,411 age-matched women without breast cancer. Date and cause of death through December 31, 2009 were assessed through the national death index and covariate data was gathered through structured interviews and medical record abstraction. Hazard ratios (HR) and 95% confidence intervals were calculated using Cox regression for overall mortality (HR) and CVD-specific death (cause-specific HR). Subdistribution HRs for CVD death were estimated from the Fine-Gray model.ResultsRisk of death was greater among breast cancer survivors compared with women without breast cancer (HR: 1.8 [1.5, 2.1]). An increase in CVD-related death among breast cancer survivors was evident only 7 years after diagnosis (years 0-7, cause-specific HR: 0.80 [0.53, 1.2], subdistribution HR: 0.59 [0.40, 0.87]); years 7+, cause-specific HR: 1.8 [1.3, 2.5], subdistribution HR: 1.9 [1.4, 2.7]; P interaction: 0.001). An increase in CVD-related mortality was observed among breast cancer survivors receiving chemotherapy.ConclusionsBreast cancer survivors are at greater risk for CVD-related mortality compared with women without breast cancer and this increase in risk is manifested approximately 7 years after diagnosis. Efforts should be made to identify risk factors and interventions that can be employed during this brief window to reduce the excess burden of CVD in this vulnerable population.

BackgroundBreast 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.MethodsDetailed 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.ResultsFour 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.ConclusionsLCA 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.

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.